Physio test 1

1. Muscle spindles signal information about the _____ and _____ of a muscle 2. Golgi tendon organs signal information about the _____ and _____ applied to a muscle Reflex arc and its components • Unlike conscious behavior, in which any one of a number of responses is possible, a reflex response is______ , because the pathway between receptor and effector is always the same. • Automatic response to change in environment o somatic and autonomic reflexes; _____ and ______ reflexes o_______ : skeletal muscle contraction o________ : smooth muscles and secretion

length and velocity load or force predictable spinal and cranial Somatic Autonomic

Stimulus intensity is coded by the frequency of action potentials Weak stimulus- _____ frequent Moderate stimulus- ____ frequent Strong stimulus- _____ frequent Graded potential •__________ results from ligand binding to receptor, mechanical stimulation temperature changes • They change the amplitude varies depending of stimulus _____ or ______ • Dissipate with distance can summate or add onto each other • Created at the dendrites ** ?? • Voltage gated ion channels are abundant in ____ _____ and in the _____ of the axon, so AP can be easily generated there (trigger zone) • In the membrane of _____ and ____ ____ of the neuron, the voltage gated Na+ channels are sparse.

less more most Local (graded) potentials: strength or frequency axon hillock membrane dendrites and cell body (soma)

Want to increase dopamine in basal ganglia—the dopamine cannot get through blood brain barrier?? • Cannot just inject dopamine but can inject _____ • Stimulate the dopamine receptors in basal ganglia and help PD

levodopa

These areas generate local (graded) potentials: -result from ____ binding to receptor, ______ stimulation, ______ changes, spontaneous change in _______ -magnitude varies from small to large depending on stimulus _____ or ______ -dissipate with ______ , can summate or add onto each other Sherwood L.,2007

ligand mechanical temperature permeability strength or frequency distance

A bands (dark) I bands (light) •The arrangement of thick and thin filaments forms____ and ____ alternating bands (striations) along the myofibril. ____- zone- contain only thick filaments • In the middle0 dark line is called the ______ —structural proteins that holds together big filament • I- band—in the middle dark line is called the _____ help align filaments o Area from two Z lines is called a _______ •___________ -____unit of skeletal muscle (Z line to Z line) • •The proper alignment of filaments within a sacromere is ensured by two proteins: (2) • _______; provides elasticity and stabilizes myosin o Helped by the ______ - helps align the actin (thin filaments) in the sacromere

light and dark H- M-Line Z-line- sarcomere Sarcomere-functional titin(the largest known protein) and nebulin. Titin Nebulin

Membrane Permeability -___ and ____ composition can affect membrane permeability • —________- cholesterol, _______ permeability Membrane Permeability proportional to Lipid Solubility / molecular size • Changing the composition of the lipid layer can increase or decrease membrane permeability

lipid and protein increase decrease

************************************ 29 There is a very large transmembrane electrochemical gradient of Ca2+ driving the entry of the Ca2+ into cells, yet it is very important for cells to maintain ________- intracellular Ca2+ for proper cell signaling • Increase in calcium concentration,____ _____?

low muscle contraction ?

•Damage to ____ ____ _____ is associated with flaccid paralysis, muscular atrophy, hypotonia (decreased muscle tone), and hyporeflexia or areflexia. Example:______ infects and selectively destroys the motor neurons cell bodies located in the ventral horn of the spinal cord. Upper motor neuron syndrome •Common causes include ____, ____, and __________. •Upper motor neurons are typically____ in nature, thus a lesion that disrupts upper motor neurons will remove inhibition, resulting in______ , hypertonia, spastic paresis (incomplete paralysis). • Symptoms and signs are completely different and sometimes different • Abnormally,______ muscle tone, more_____

lower motor neurons Poliovirus stroke, tumors, and blunt trauma inhibitory hyperreflexia INCREASE EXCITED

Vesicular Transport • Some molecules are too large for carriers • Many ______ that are too large to enter or leave cells through protein channels or carriers move in and out the cell with the aid of _____ created from the cell membrane o They _____ with the membrane • To import large molecules cells use _____ and ______ • Material leaves the cells by exocytosis

macromolecules vesicles fuse phagocytosis and endocytosis

Sympathetic division •_____ ____ and ______ increase and blood is ______ to the skeletal muscles, heart, and liver by ______ of arterioles in the skin and viscera . • Tissue metabolism is directed toward energy utilization by _______ in the liver and ____ in adipose tissue. • ____ ____ contraction of sphincters in the GI and urinary tracts, dilation of the bronchioles and pupils. Parasympathetic division - The functions of the parasympathetic division generally act to ____ and ______ energy reserves during the time of rest. * most come from the ______ nerve •SLUDD responses (SLUD6) • -_______________________ o decreased ____ o decreased _____ of airways o decreased diameter of ____ (lens - near vision) o dilation of _____ ________ (erection) para- large amount of watery saliva

Heart rate and contractility redistributed constriction glycogenolysis lipolysis Smooth muscle: conserve and restore Vagus Salivation, Lacrimation, Urination, Digestion & Defecation and 3 "decreases" + 1 increase HR diameter pupil erectile tissues

Function: Anchoring Location: cell- matrix junction Type: __________- Membrane protein: ______ Cytoskeleton fiber: ________ (intermediate filaments) Matrix protein: _______

Hemidesmosome Integrin Keratin Laminin

________ —the water will move OUT of the cell • The cell will shrink, the volume will decrease ________ —the water INTO cell same was OUT Volumes remains the ____ _______ Water moves INTO cell Volume increases Tonicity- only relative term—not units of measurements • Compares solution to cell

Hypertonic Isotonic same Hypotonic

Body fluid compartments • One functional unit the fluid in all the cells, we can one functional fluid compartment called ____ o _____- outside cell but still inside the body o In between, is the _____ _____ o ECF- _____ and ____ _____ with blood vessels in between

ICF ECF V Plasma and Interstitial fluid

Cell Membrane Proteins •__________- deeply embedded in phospholipid bilayer, spanned across the membrane • _______ -loosely attached to the surface of the cell membrane via an ______ _____ • Lipid anchored -attached to a _______ _____

Integral (transmembrane) Peripheral integral protein lipid tail

Organism in Homeostasis • External change and Internal Malfunction o ______ change results in loss of homeostasis o Response attempts to compensate •The study of body functions in a disease state is known as _________. •____ _____ is a systemic metabolic disorder characterized by abnormally high blood glucose concentrations; it affects ______-% of the U.S. population. • The whole collection of diseases -______disease - affects numerous, all body systems

Internal pathophysiology Diabetes mellitus ~8.3 systemic

Clinical application: Increase of GABA-mediated synaptic inhibition • Barbiturates are used to manage the seizures and also as sedatives and anesthetics • Bind to GABA A receptors,______ receptor, GABA gated channel, increases membrane permeability to Cl--- hyperpolarization—_____ • With Barbiturates—channel opens widens—enhances ____ permeability o Amplitude of______ is larger o Decrease ability to create an AP even further o Greater inflow of Cl- causes prolonged______ of the postsynaptic neuron

Ionotropic IPSP Cl- hyperpolarization inhibition

•____ and ______ molecules move freely through nuclear pores, but _____ and _____ must be transported by processes that use energy. It allows the cell to restrict the DNA to the nucleus and to restrict various enzymes to either cytosol or to the nucleus. RNA and proteins are transported by ?????? 62 • Cells assemble into the larger units called ___ . • The study of tissue structure and function is known as _____ .

Ions and small proteins and RNA tissues histology

Osmolarity: Comparing Solutions TABLE 5-5 *** 50 _____ : same number of particles in liters of solution _______ : less amount of particles _______: more amount of particles Only the ______ of particles not the nature of the particles We need to know properties of the molecules, and the membrane itself

Isomotic Hyposmotic Hyperosmotic amount

Astrocytes TAKE UP ,(3) SECRETE: ____ ____ HELP FORM -____ _____ ___ Provide: __________ also are a source of neural stem cells

K+_, water, and NT Neurtropphic factors blood brain barrier substrates for ATP production

Cytoskeleton ?? 55 Tumor diagnoses -origin of the tumor • The filament the protein is called _____ —epithelial cells Clinical correlations: Keratins form intermediate filaments in various epithelial cells. • Presence of keratin in cancerous cells indicates _____ _____tumors - carcinomas. Tumor from muscles - ______ Fibroblast cell ______ ?? nerve cell _____ mesenchymal cell: ___

Keratin epithelium- derived dynein fermentin neurofilaments Vimentin Mesenchymal cells are able to develop into the tissues of the lymphatic and circulatory systems, as well as connective tissues throughout the body, such as bone and cartilage. A sarcoma is a malignant cancer of mesenchymal cells

Summary of current therapies for Parkinson Disease • ______ is a prodrug - immediate metabolic precursor of dopamine (DA), can cross the BBB while DAcan not • _____ % of Levodopa actually enters the brain due to extracerebral metabolism •_____ ______ can be reduced and amount of levodopa that reaches CNS may be increased by administering peripheral DOPA decarboxylase inhibitor (carbidopa) or COMT inhibitors.

Levodopa 1-3 Extracerebral metabolism

Fast Pain • ______ myelinated • ______ Diameter • Nociception • Mechanical, thermal, chemical Slow Pain • _____ • _____ diameter • Innocuous temperature, itch, nociception • Mechanical thermal chemical Slide 29 • Depolarized threshold - transmit information to the Spinal cord • Withdrawal reflex - conveyed to ____ tract

Lightly Medium Unmyelinated Small spinothalamic tract

Phospholipid Bilayer _____ - major component, form bilayer ______ - the most abundant type • Both hydrophilic and hydrophobiic Phospholipid molecules have ___ heads and ____ tails • The ___ _____ is variable polar group Polar head- _____ Nonpolar Fatty acid tail- _____

Lipids Phospholipids polar nonpolar R group hydrophilic hydrophobic

Stabbed in the back during fight, to the left half of the spinal cord T11 which of the following neurologic deficit would result •____________________ • Vibration (DCML) - contralateral above the medulla

Loss of pain sensation in the right leg

_______ : Act as digestive system of the cell • Use powerful ____ _____to break down bacteria or old organelles • Lysosomal enzymes are active at pH __-___ o Acidic pH o If they get out, they cell remains uninjured because of active at normal body pH • Contain very power ____ enzymes • Hydrolyipic o___ _____ from Golgi: carry inactive hydrolytic enzymes

Lysosomes digestive enzymes 4.8-5 digestive Transport vesicles

Multiple Sclerosis (MS): Myelin-Going, Going, Gone •______ is autoimmune disease in which the body defense system erroneously attacks the myelin sheath surrounding the nerve fibers •Hardened scar known as ______ (meaning hard) forms at the sites of ____ _____ •These scars interfere with and can eventually block AP propagation in the axon •The symptoms vary considerably depending on the location and extent of the myelin damage; most common symptoms include visual problems, tingling and numbness, muscle weakness, impaired coordination and gradual paralysis

MS sclerosis myelin damage

Stimulus Property: Location of stimulus WHERE? _____ of _______ Distinguished by the location of the activated receptor field and the specific pathway which is activated to transmit the information to the area of the somatosensory cortex representing the particular location ____ _______ Intensity of Stimulus (stimulus strength) HOW MUCH? Mechanism of Coding: Distinguished by the _______ of APs initiated in an activated afferent neurons and the ______ of receptors (and afferent neurons) activated --_______ coding- strong stimuli more sensory receptors are activated in response ?

Mechanism of Coding: Stimulus Property: frequency number Population

_______ are droplets of phospholipids : Lipid absorption in the gut : Digestion of dietary fats ______ have an aqueous center • Used for delivery of drugs (especially hydrophilic) •Drug delivery - _____ compounds permeate cell membranes by diffusion • Example: cream for face

Micelles Liposomes lipophilic

Neuroglia of CNS • ______ -Immune defense cells of CNS • -Upon infection or injury retract their branches, round up and act as specialized _______ and ____ _____ cells - Migrate to infected tissue or cells • -Move into affected area, remove any invaders or tissue debris, release destructive chemicals • Excessive release of _____ form microglia is suspected to contribute to neuronal damage seen in ______ , • Alzheimer's disease, multiple sclerosis and other neurodegenerative diseases

Microglia macrophages antigen presenting chemicals stroke

"______ " neurons respond not only to a particular action of the monkey but also to the sight (or sound) of another individual performing the same action. (video on mirror neurons: http://www.pbs.org/wgbh/nova/body/mirror-neurons.html) Science. 2002 Aug 2;297(5582):846-8. • Why we can get so worked up by watching other people • Watching sports games • Primes us to imitate what we see "_____ _____ " in motor control •Modulate the output of the descending pathways without directly causing motor output

Mirror Side loops

________ •The sites of most ATP generation, "cell's powerhouse"; the number of mitochondria in particular cell depends on the cell's energy needs Double Wall Outer—keeps _____ Inner- ____ ATP generation # varies on cell____ and _____ o More _____ more mitochondria Muscle vs fat cell

Mitochondria shapes Cristae type and activity metabolic

Muscle Diseases • Dysfunction can arise from a problem with the signal from the nervous system, miscommunication at the neuromuscular junction, or from defects in the muscle. •_____________ sustained painful contraction of skeletal muscles -caused by ________of the motor neuron: as it fires repeatedly, muscle fibers of its motor unit go into state of painful sustained contraction. -sometimes can be relived by forcibly stretching the muscle; stretching sends sensory information to the CNS that inhibits the motor neurons.

Muscle cramp ("charley horse")- hyperexcitability

Internal Structure of a Skeletal Muscle Cell ____ _____ -muscle cells _____ -cell membrane _____ -cytoplasm _______ -mitochondria ____ ____ : Smooth endoplasmic reticulum

Muscle fibers Sarcolemma Sarcoplasm Sarcosomes Sarcoplasmic reticulum

____________-autoimmune disease • MG is characterized by painless fatigable muscle weakness. It is caused by autoantibodies against ___________ recepts

Myasthenia gravis (MG) nicotinic acetylcholine receptor (AChR).

Neuroglia of PNS ____ —major structure component is phospholipids Impermeable to ions Acts as an _____ , prevents leakage of ____ _____ •Schwann cells cover ____ and _____ axons in the PNS • •Unmyelinated axons are surrounded by Schwann cells that don't form myelin o In the PNS, _____ wrap around multiple axons o Several axons with no myelinated • Myelinated axons: -Myelin is composed primarily of _____ -Myelin protects, acts as _____ , increases ____ _____ o Single axon • -Nodes of Ranvier •Myelinated axons conduct an action potential ______ than unmyelinated axons

Myelin insulator electrical charge myelinated and unmyelinated single lipids insulator conduction velocity faster

slide 37 Adrenergic Receptors: they are 7G proteins?? *** • Activated by ____ . Then EP • Except for certain blood vessels and smooth muscle of some organs o E > NE • Heart muscle and kidney __________ Primary disorders of the autonomic division are rare. Diabetic autonomic neuropathy is relatively common. Begins as sensory neuropathy, with tingling and loss of sensations in the hands and feet, ~ 30% of patients will develop autonomic neuropathies => dysfunction of cardiovascular, GI, urinary and reproductive systems (abnormal heart rate, constipation, incontinence, impotence).

NE =E Noeph except for GI tract and pacrease

• Secondary active transport uses the energy of one molecule moving down its concentration gradient to push other molecules against their concentration gradient. The most common secondary active transport systems are driven by ______ concentration gradient. • Na+-glucose secondary active transporter (SGLT) uses Na concentration gradient, created by Na+-K+-ATP-ase to transport _______

Na+ glucose

______ is one of the standard drugs used in the symptomatic treatment of myasthenia gravis. Normally, ____________ metabolizes Ach into choline and acetate. Following AChE inhibition by _______ , more Ach is available to activate receptors at the motor end plate.

Neostigmine acetylcholinesterase (AChE) neostigmine

The Action Potential (AP) of a skeletal muscle fiber begins at the ________ ________, where the terminal of a motor neuron contacts and forms a _____ with the muscle fiber. Neuromuscular Junction (NMJ) •___ -___ _____ - post synaptic - muscle fiber • Release _____ in the synaptic cleft by ____- • Depolarization • AP • Inhibited by the _______

Neuromuscular Junction (NMJ) synapse Motor end plate Ach exocytosis Acetlycholnesterase

Nervous system histology Two cell types: 1. ______ : highly specialized, excitable cells, generate action potential 2._____________ : do not initiate or conduct nerve impulses, important for viability of the neurons, support neurons physically and metabolically, actively modulate synaptic function (90% of the cells in the CNS) metabolic and structural support, synaptic transmission, In the CNS • 4 types of glial cells in CNS: (4) • 2 types of glial cells in PNS: (2)

Neurons Supporting cells or Neuroglia astrocytes, oligodendrocytes, microglia, ependymal cells Schwann cells, satellite cells

_______ : The function is to degrade long chain fatty acids and potentially toxic foreign substances. Reactions that take place inside peroxisomes generate ______ , a toxic molecule. • The peroxisomes rapidly convert H2O2 into ____ and ____ • Different stack of enzymes from lysosomes o Hydrogen peroxide to oxygen and water Break long chain ____ _____ and ____ substances

Peroxisomes H2O2 O2 and H2O. fatty acids toxic

______ requires energy from ATP for the movement of the cytoskeleton and for the _____ transport of the vesicles. • In humans phagocytosis occurs only in certain types of ____ ____ ____ which specialize in "eating" bacteria and other foreign particles. • ACTIVE transport because it uses energy from ATP to move __ ____ o Only WBC's ?

Phagocytosis intracellular white blood cells, cytoskeletal fibers

Skin (usual Stimulus) 1. ______ sensory neurons 2. _____ sensory path to somatosensory cortex of brain 3. ______ sensory neuron 4. Kidney (uncommon stimulus)

Primary Ascending Secondary

• Cell body are in the ____ _____area --cerebral cortex o Axons run all the way down to Spinal cord o Lateral Corticospinal tract - stops at _____ _____ Fine movement of digits in the hand o Anterior Corticospinal tract- ______ muscles o But BOTH latera anterior are______ pathways, cross midline and go to contralateral side o Later crosses at ____ ____ o Medial crosses at Spinal • If Primary Motor cortex damage, the____ side move deficient

Primary motor Medulla Oblongata Trunk CROSSED Medulla Oblongata opposite

________ is the sense of the body's position in space based on specialized receptors that reside in the muscles and tendons • Muscle spindles and Golgi tendon organs -____ ______ Consist of specialized muscle fibers called intrafusal fibers inside the fibrous capsule • Sensory axons (large, myelinated, very fast conduction speed) are wrapped around intrafusal fibers in the middle portion • Provide information to CNS about the ____ _____ and the_____ with which muscle_____ is changing • The central region of muscle spindle is not______ , but there are contractile_____ at each end • Motor supply to contractile filaments within muscle spindle is provided by ____ ____ ____ • Muscle spindle: more for sensory receptions about muscle ____ nd _____ _and_____ of muscle

Proprioception Muscle spindles: muscle stretch (length) speed length contractile filaments g-motor neurons stretch and length velocity

Active Transport • cell does use energy 1._____ _____ Sodium Potassium pump; hydrogen pump in stomach 2. _______ 3. ________ • UP the concentration gradient • ___ to _____ , require energy • Energy- high energy ______- bonds of ATP

Protein Pumps- Endocytosis Exocytosis LOW TO HIGH phosphate

NEUROPHYSIOLOGY SYNAPTIC TRANSMISSION Anastasia Mashukova, PhD E-mail: [email protected] Objectives PART I: •Nervous system anatomical and functional organization •Nervous system histology (neurons and supporting cells) PART II: •Action potential, graded potential, EPSP and IPSP, mechanisms of electrical signal propagation Nervous system functions •_____ , ____ ,______ and rapidly _____ information about the internal and external environment from one part of body to another • Neurons in the nervous systems are linked together to form ____ that have specific functions • Awareness, perception, memory, language, learning, thinking and behavior • Controls ___ ____ and the ____ of many glands • Modulates _____ system • Regulates homeostasis in coordination with the ____ ____

Receives, processes, encodes transmits circuits muscle movements secretions physiological endocrine system

• 1. Sensory____ • 2. Sensory______ (AFFERENT) • 3._____- • 4. Motor______ (EFFERENT) • 5. ___ ______ Reflex response is always______ and the same

Receptor neurons Interneuron Neuron Effector organ predictable

-____ _____ is a term used to describe the phenomenon of pain perceived at a site other than the actual site of tissue injury • Example:_____ damage to heart muscle during a heart attack is felt in the neck, shoulders and back rather than the chest • The mechanism causing referred pain is unknown Referred pain • Pain in internal organs is often sensed on the surface of the body, a sensation known as____ -____ • One theory of referred pain says that Nocicrepectors from several locations converge on a single -____ -____ in the spinal cord • Pain signals from the skin are more common than pain from ____ ______ and the brain associates activation of the pathway with pain in the skin • Should, arm, heart- left • Liver with gall bladder- right abdominal • Appendix, Stomach, Small Intestine, Colon, Ureters

Referred pain ischemic referred pain ascending tract V

Types of Neurons • Functional classification -_______ conduct action potentials toward the CNS (coming) -_______ conduct action potentials away from the CNS (going) - - ______ or _____ neurons: within CNS from one neuron to another • Structural classification - Multipolar, bipolar, unipolar - Number of ______ from the cell body • Specific _____ , _____ , and/or _____ - cholinergic, adrenergic, serotonergic, GABAergic, glutaminergic _ the NT they release

Sensory or afferent: - Motor or efferent: Interneurons or association extensions location function neurotransmitter

Motor control •____ _____ provide information about the environment, which is then used to produce action to change the environment • Sometimes the pathway from sensation to action is direct, as in a______ • In most cases ____ ____- occurs to make actions adaptive and appropriate for the particular situation • The final output is a set of______ to certain muscles in the body

Sensory receptors reflex cognitive processing commands

Somatosensory System •____ _____ system conveys sensations from the skin: touch, vibration, pain, and temperature. •It also includes _____ , which relates to sensory information from the musculoskeletal system (recall our lecture on motor systems). •Irrespective of their modality all somatosensory information from limbs and trunk is conveyed by ___ _____ _____ neurons. (adjacent to spinal cord) only • Afferent sensory neurons—convey the somatic sensations • Called a _______

Somatic sensory proprioception dorsal root ganglion detmatone

The ability of a carrier molecular to transport only one type of molecule or a group of closely rated molecules is called • _____________ The Body Is Mostly Water • The standard 70 kg (154 pound) male has ____ % of his total body weight, or 42 kg, in the form of water. • Women have _____ water per kg of body mass because women have more ____ _____ • As you get older, water content ____ infant you have ______ water %

Specificity 60 less adipose tissue. decreases more

•______ refers to the ability of the carrier to move only one molecule or only one type of chemically related molecules. • One specific chemical across the membrane •____ family of transporters move 6-carbon sugars, hexoses (e.g. glucose, mannose, galactose, fructose)—by facilitated diffusion • Binding sites of GLUT recognize hexoses, but they will not transport disaccharide maltose: specific for naturally occurring 6-carbon monosaccharaides.

Specificity GLUT

________________ tract conveys pain and temperature sensory input • 3 neurons that synapse in CNS • Afferent sensory neuron goes to Spinal Cord • Immediately synapse with the second neuron of the pathway, has cell body in gray matter of the _____ ____ • Then all the way to the thalamus • Also cross pathway, but at ____ _____ • Damage is Always on the _____ side of the body • Crosses at the spinal cord-- ______ —relay information except olfactory information before it gets to cortex Ipsilateral means - same side

Spinothalamic (anterolateral) Spinal cord spinal cord CONTRALATERAL Thalamus

Fast twitch muscle fibers? • Marathon runner or sprinter? o Sprinter -_____ : fast twitch, fatigable fibers, predominate ___ ____ slow twitch, fatigue resistant fibers predominate

Sprinter Marathon runner-

Substance P •___________ (P for Pain) is an 11-amino acid polypeptide [ Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met NH2] of the tachykinin neuropeptide family that functions as a neurotransmitter and as a neuromodulator • One of the important neurogenic neurons, ______ mediator •The receptor for Substance P is the neurokinin 1 receptor (NK1-receptor, NK1R) which belongs to the tachykinin receptor subfamily of GPCRs •In the CNS system, substance P has been associated in the regulation of mood disorders, anxiety, stress, reinforcement, neurogenesis, respiratory rhythm, neurotoxicity, nausea / emesis and pain •Naked mole rats lack Substance P and do not feel certain type of pain • Also vomiting reflex

Substance P polypeptide

************************************ 16 (2) Fick's Law of Diffusion says: Rate of diffusion is proportional to (______) Rate of diffusion/surface area • Membrane thickness—_____ in most physiological situations, does not significantly affect • ____ ______ is the most complex factor ??? • Concentration gradient ??

Surface area * concentration gradient * membrane permeability / membrane thickness constant Membrane permeability

Chemical Synapses • Presynaptic terminal - o-__ _____ contain chemical messenger neurotransmitter (NT) • ___ ____ - Space between presynaptic cell and postsynaptic cell - Neurotransmitter____ o Much larger than chemical synapse • Postsynaptic membrane - Neurotransmitter receptors •____ (one-way)

Synaptic vesicles Synaptic cleft diffusion Monodirectional

______ transmit electrical change into sarcoplasm DHP = dihydropyridine L-type calcium channel RyR = ryanodine receptor-channel 1. Action potential generated is propagated along the sarcolemma and down the ___ -_____ 2. Action potential triggers Ca2+ release from ____ ____ of SR 3. Calcium ions bind to _____ : troponin changes shape, removing the blocking action of _____ ; actin active sites exposed 4. ______ ; myosin cross bridge alternatetly attach to actin and detach, pulling the actin filaments toward the center of sarcomere; release of energy by ______ hydrolysis powers the cycling process 5. Removal of Ca2_ by ____ -_____ into SR after the action potential ends 6. _______ blockage restored blocking actin active site; contraction ends and muscle fiber _____

T-tuble- T-tubules terminal cisternae troponin tropomyosin Contraction ATP active transport Tropomyosn relaxes

The Contents of the stomach lumen are outside the body- T/F • The _____ organs, such as heart, lungs, blood vessels and intestines, create another set of compartments within the body • The lumen of digestive tract is ____ the body • The interior of any hollow organ is called its ______ . • Lumen of the digestive tract—pH in the stomach lumen is ____ . o The normal pH is 7.0-7.4 o When microorganisms get into the internal environment, they can become o Contents on the ____ ____ are outside of the body

TRUE hollow outside lumen 2 digestive tube

________ is a toxin that blocks voltage-gated sodium channels, what effect does this substance have on the function of neurons • ____________ The ______ : Junction between two neurons - Presynaptic neuron - Postsynaptic neuron • Site where an action potential in one cell affects the production of an action potential in another cell I. ______ Synapses (pass electrical signals)—small number II. ______ Synapses (use neurotransmitters)—most One AP of a neuron affects the AP of the other—___________

Tetrodotoxin Neurons are not able to generate action potentials Synapse Electrical Chemical synapse

Rates of AP conduction 1. Which do you think has a faster rate of AP conduction - myelinated or unmyelinated axons? • 2. Which do you think would conduct an AP faster - an axon with a large diameter or an axon with a small diameter?

The answer to #1 is a myelinated axon. If you can't see why, then answer this question: could you cover the distance of 100 ft faster if you walked heel to toe or if you bounded in a way that there were 3 ft in between your feet with each step? The answer to #2 is an axon with a large diameter. If you can't see why, then answer this question: could you move faster if you walked through a hallway that was 6 ft wide or if you walked through a hallway that was only 1 ft wide?

______ _____ Discovery that astrocytes are capable of releasing chemicals similar to neurons (gliotransmitters) upon stimulation, and the fact that most synaptic junctions are enveloped by astrocytic processes, adds another dimension to the two-part junction, making it the "tripartite synapse". Charts slide 30 **

Tripartite synapse.

______ : relaxed- covers the binding ste Troponin: 3 subunits • One tropomyosin, Ca+ and ?? Slide 11 • Muscle fiber relaxed; no cross-bridge binding because the cross- bridge binding site on actin is physically covered by the-___ ______ complex • Muscle fiber excited: released _____ binds with _____ , pulling _______ complex aside to expose cross-bridge binding site; cross-bridge _____ occurs • Binding of actin and myosin cross bridge triggers ____ _____ that pulls filament inward during contraction

Tropomyosin troponin-tropomysoin CA+ troponin troponintropmysoin binding power stroke

Functional classification based on the evolution of cerebellar functions: • _________ phylogenetically the oldest part, has vestibular connections and is concerned with equilibrium and eye movements. • ________ that receives proprioceptive input from the body as well as a copy of the "motor plan" from the motor cortex. By comparing plan with performance, it ______ and _____ movements that are ongoing= _____ function. • ______ is the newest from a phylogenetic point of view, reaching its greatest development in humans. It interacts with the motor cortex in planning and programming movements. o Playing piano and swinging baseball bat

Vestibulocerebellum Spinocerebellum smoothes and coordinates comparator Cerebrocerebellum

1. Deletions or duplications producing frameshifts in the gene coding dystrophin, located on the _____ chromosome 2. Diminished synthesis of the mRNA of dystrophin 3. Low levels or absence of _____ 4. ________ integrity of the muscle cells is affected 5. _______ stress the muscle cells and they gradually die 6. Progressive, usually___ ___ weakness

X dystrophin Structural Contractions fatal muscular

Duchenne muscular dystrophy * Mutations in the genes encoding various components of the muscle large dystrophinglycoprotein complex, are a prominent cause of muscular dystrophies. * is necessary for structural integrity of muscle fibers Becker Muscular Dystropy- More mild > Duchene muscle dystrophy (DMD) DMD is an ___-_____ inherited disorder • On the X chromosome . distal mengine ? • Males are at higher risk • Females have two copies of X chromosome

X-linked

What mechanism ensures AP propagation in one direction? • •During ____ _____ _____, the portion of the membrane that has just undergone an action potential cannot be restimulated. This corresponds to the time during which _____ channel gates are not in their resting confirmation. o Cannot be stimulated AT ALL, not even by normal events • •During __________ AP can be generated, but it will require considerably stronger stimulation than usually necessary. It happens because _____ than normal voltage-gated Na+-channels are in a resting position and K+ is still leaving through its ______ -to-close channels during the undershoot. o The area can be stimulated to generate another AP but need a ____ stimulus

absolute refractory period Na+- relative refractory period fewer slow STRONG

By blocking _______ release at the NMJ, botulinum toxins cause flaccid paralysis. The mortality of botulism is usually secondary to paralysis of the respiratory muscles. • Uses a _____ complex* • Exocytosis and release of Ach in synaptic cleft • With Ach release—no transmission at junction

acetylcholine Snare

Organization of a Muscle Fiber: Myofilaments Thin filaments-mainly ____ Thick filaments-chiefly _____ ____ ____ form cross bridges between thick and thin filaments. Each cross-bridge has two sites crucial for muscle contraction: _____ -binding site and ____ -binding site. • 2 subunits - heads • Essential for interactions with _____ filaments—crossbridges o Two sides for binding—____ and _____ binding site • G- Actin molecule—and for F- actin come together • Binding site for attachment with myosin cross bridge

actin myosin Myosin heads ATP actin actin and ATP

•During muscle contraction, ____ and _____ filaments of fixed length slide past one another in an _____ -requiring process, resulting in ____ ____ • _____ filament slide along ____ filaments toward ____- • Z lines move closer together and the sarcomere shortens • Length of A band does not change • The ____-___shortens as the ___ ____comes closer together

actin and myosin energy muscle contraction. Thin thick M- line I band Z lines

Objectives •Action potential, graded potential, EPSP and IPSP, mechanisms of electrical signal propagation Neurons communicate by producing electrical impulses called _____ _____action potential tutorial • Behavior of the ____ _____, which allows us to explain the electrical advice • ___- _____ open Na+ ions enter cell depolarizations changes cell, more o_________-- FEEDBACK LOOK o Depolarizes even more then continues • Has to be ______ the a certain degree to create and AP is called the ____ _____ o Usually a result from a stimulation of a neuron , activation of certain membrane ??? o If it depolized to threshold—the AP is generated o AP is ____- and _____ in potential but opening of Na+ channels

action potentials ion channels Na+ channels POSITIVE depolized threshold potential rapid DECREASE

Sympathetic pathways use____ and _______ • _______ receptor Parasympathetic pathways use ______ • _____ receptor Autonomic System • Parasympathetic _____ and _____ _ _______ Receptors Smooth muscle, cardiac tissue, secretaory glands • Sympathetic o ____ and _____ o Release _____ into blood ( noo receptors) o _____ receptors and ____ receptors (sweat gland M.)

actylcholine and norepinephrine Adrenergic acetylcholine Muscarinic • Cranial and spinal Muscarinic Thoracic and lumbar Epi/NO Adrenergic Muscarinic

Receptor Adaptation • •Some receptors have the ability to diminish the extent of their depolarization despite sustained stimulus strength, a phenomenon known as _____ . • •A receptor can only transduce a stimulus that is applied to a ____ _____ or a receptive field of this receptor. • No sensory adaptation is called ____ -_____ • Amplitude of receptor potential Response decreases= slowly adapting • Amplitude of Receptor potential increases rapidly o The ______ department o Touch receptors in skin Can't continuously feel watch But have OFF receptors o Prevent flood of irrelevant sensory information

adaptation restricted area, Tonic response olfactory

Function: Anchoring Location: Cell-cell junctions Type: ______ junction Membrane proteins: _______ Cytoskeleton fiber: ____,

adherens Cadherin Actin

The____ ______ which forms the small core of the adrenal gland develops from the same _____ tissue as sympathetic neurons and is a neurosecretory structure. • They are axon less • Adrendal cortex is a true _____ gland • Adrenal medulla is a modified _____ ganglion o They are axon less The _________ (no axons) • Is a modified postganglionic sympathethic neuron o So they release o EPI/NE—neurohormone in the blood Para—polynargiic ?????? Varicosities in Autonomic Neurons •NT is synthesized in varicosities and packaged in ______ •Target cells do not contain clusters of NT receptors at specific sites. •NT is released to ____ -_____ to diffuse to wherever the receptors are located => less directed form of communication •Single postganglionic neuron can affect a large area of target tissue. Norepinephrine Release at a Varicosity of a

adrenal medulla embryonic endocrine sympathetic Chromaffin vesicles interstitial fluid

Action potentials are _____________ response • So long as threshold is surpassed, additional increases in stimulus strength do not lead to increases in the amplitude of the AP - "all-or-none law" (refers to the fact that there is no "in-between" AP). o ______ generate by the same neuron is always the same o If threshold is not reached, nothing will happen o AMPLITUDE IS ALWAYS THE _____ • The neuron either does not respond (in the case of sub-threshold stimuli), or it will generate a full-fledged, all-or-none AP (in the case of supra-threshold stimuli). • Action potential ______ determines the strength

all-or-none r Amplitude SAME frequency

********************************** 68 • There are three main types of cell junctions: ______ junctions, __________(gap) junctions and _______junctions (tight junctions or zonula occludens) • Anchoring Junctions Connect the Cytoskeleton of a Cell Either to the ______ of Its Neighbors or to the _____ _____ o Major function is to stick cells together or to ____ o By linking ____ _____ together o Matrix uses ____ ____ proteins o ??????????? Cell - cell anchoring junctions • ______ junctions and _____ : contain cadherins that mark tissues with low ______ activity) • Link together ____ filaments

anchoring communicating occluding Cytoskeleton Extracellular Matrix matrx Cytoskeleton filaments intracellular anchor Adherens desmosomes ACTIN proliferative

Cholesterol Important constituent of _____ cell membranes (prokaryotic cell membranes lack cholesterol) - synthesized and excreted by ____ ____ - serves as a precursor for ____ _____ and ____ ____ • ???? Cholesterol -increases "tightness" of membranes : ______ permeability to water and urea -lowers membrane ____ • Helps establish the membrane ______ • _____ membrane fluidity • Increase cholesterol—_____ membrane permeability

animal liver cells bile acids steroid hormones decreases fluidity structure LOWERS decrease

The motor system hierarchy consists of 3 levels: • Level 3 (Highest level of control) resides in areas of_____ ______ and the ____ _____ which determine the______ of movements o Called the motor association cortex and basal ganglia • Level 2 consists of ___ ____ and ____ which determine the correct____ of commands, which allow the goal to be achieved • Level 1 (Lowest level of control) consists of ___ _____ in the spinal cord, which function to_______ descending commands

association cortex basal ganglia, goal primary motor cortex and cerebellum, sequence neuronal circuits implement

Muscle Diseases •With prolonged inactivity (e.g. when a limb is immobilized in a cast), the skeletal muscles _______ . If activity is resumed in less than a year, the fibers usually regenerate. •If the atrophy results from ______- motor neuron dysfunction, therapists try to maintain muscle function by administering _______ impulses that directly stimulate the muscle fibers. • Blood supply decreases • If cause my motor neurons, electoral stimulation to muscle fibers

atrophy somatic electrical

•By the time the original site has recovered from its refractory period and is capable of being restimulated by normal current flow, the AP has been rapidly propagated in the forward direction only and is so far _____ , that it can no longer influence the original site. •The refractory period ensures the ______ propagation of the action potential down the axon away from the initial site of activation. Which ions are high in concentration inside the cell compared to outside • ______ -cation inside the cell • _____ - outside the cell

away one-way Potassium Sodium

Motor Executions • To medial descending systems • To lateral descending systems Motor Planning • To motor and premotor cortices x___ and _____ movements • The vestibular Nuclei

balance and eye

Ependymal cells are a source for neural stem cells and create ______ between compartments

barriers

In order to prepare that patient for surgery aimed to remove the tumor, what types of ANS medications may be used to stabilize her blood pressure within normal range • Beta-blockers—Competition antagonists of beta-adrenergic receptors o Inhibit sympathetic branch of internal organs o Muscarinic receptor—______ nervous system o In hear—____ _____ —inhibit sympathetic branch in the heart

beta blockers parasympathetic

Carrier mediated transport competition • A transporter can move one or several types of substrates, but those substrates will compete with one another for_____ _____of the transporter. • GLUT transporters move ____ sugars, but each GLUT transporter has a "preference" for one or more hexoses, based on its binding ____ . • If the competing molecule is not transported but blocks the transport of another substrate, it is a _____ ______

binding site hexoses affinity competitive inhibitor.

Gray matter contains the nerve cell _______ )] White matter contains the bundles of ____ -______ _____ root: carries sensory (afferent) information to CNS. ______ root: carries motor (efferent) information to muscles and glands. • Characteristic pattern of gray and white matter •Grey matter (butterfly): dorsal horn, ventral horn and intermediate zone

bodies myelinated axons Dorsal Ventral

ANATOMY Study of ____ ____ Small Intestine _____ • Building block of life (every organism is made up of at least one cell) • The whole organism is generated by cell divisions from a _____ cell • The single cell is the vehicle for the _____ ____ that defines the species

body structure Cell single hereditary information

Major cavities of the human body •The cavities are separated from one another by ____and ____, and they are lined by ____ _____ • Cranial Cavity o Skull • Thoracic cavity sac- Thorax o Pleural sac o Pericardial • Diaphragm • Abdominopelvic cavity o Abdominal cavity o Pelvic Cavity

bones tissues tissue membranes.

Clinical features of PD Four cardinal features: • ________ o slowness and poverty of movement ____ ____ o stiffness and resistance to limb movement caused by _____ muscle tone ____ _____ o which usually abates during voluntary movement • impairment of ____ _____ leading to disturbances of gait and falling • Illustration of Parkinson disease by William Richard Gowers, which was first published in A Manual of Diseases of the Nervous System(1886). o PD is characterized by rapid ___ ____ and a ____ -____ posture when walking

bradykinesia • muscular rigidity increased • resting tremor postural balance shuffling steps forward-flexed

• Loss of E-cadherin function or expression has been implicated in ____ ____ and ______ . E-cadherin downregulation decreases the strength of cellular ______ within a tissue, resulting in an increase of ____ _______ . • Link together the ______ filaments loss of ______ —increase in migration of cancer cells and migration • Cancer cells become more side, cross the basal lamina, into tissue • High levels- mark with lower ??? activity

cancer progression metastasis adhesion cellular motility intermediate (actin) Cadherin

Glycolipids Lipids with attached _______ , chains of sugar molecules -present on the _____ surface of cell membrane -can function as (3) 1. Membrane splits into layers in freeze-fracture electron microscopy 2. Intracellular surface of membrane 3. Cholesterol molecules insert themselves into the _____ layer a. Abundant b. Important physiological functions 4. Lipid tails form the ______ layer of membrane 5. Phospholipid heads face the ____ ______ and _____ compartments

carbohydrates external antigens, cell identification markers (blood groups), receptors (cholera toxin lipid interior aqueous intracellular extracellular

Secondary Active Transport SGLT 1. Na+ binds to _____ a. Carrier open to _____ side b. High sensitivity to ____ c. Changes protein _______ 2. Na+ binding creates a site for _____ a. Changes _____ again 3. Glucose binding changes carrier conformation 4. Na+ released into _____ . Glucose follows. a. Open of Intracellular ?? b. Glucose also ? For each Na+ that goes into cell, the _____ goes against their concentration gradient

carrier lumen Na+ confirmation glucose confirmation cytosol Glucose

Cytoskeleton helps transport materials into the ____and within the _____ • Myosin bind to _____ fibers and are best known for their role in muscle contractions • ____ and ______ are are associated with movement along microtubules Kinesin powers ______ TRANSPORT Dynein powers _____ TRANSPORT

cell cytoplasm actin Kinesins and dynein's ANTEROGRADE RETROGRADE

Universal • Each cell is surrounded by the X_____ ____ • Separates the ____ and ____ Membranes in the body • The ______ membrane is a tissue that surrounds the heart o Seen magnified, the PM is a layer of flattened ____ ______ supported by CT o Each cell of the PM has a _____ ______ surrounding it o The_____ ____ is a phospholipid bilayer •A membrane can refer either to a thin ____ _____, such as the pericardial membrane, or to the _____ ______ surrounding every cell in the body (the cell membrane or plasma membrane).

cell membrane ICF and ECF pericardial epithelial cells cell membrane tissue layer phospholipid bilayer

Lipid bilayer is semi-permeable • Whether or not a molecule can cross the plasma membrane depends on both: properties of the _____ _____ and properties of the _____ . Two properties of a molecule influence its movement across cell membranes: the ____ of a molecule and its ____ _____ • Very _____ molecules, and those that are ____ _____ can cross the lipid bilayer. • Larger and less lipid soluble molecules usually do not enter or leave a cell unless the cell has specific _____ _______ to transport them. Very large molecules enter and leave cells in ______ . • Depends on properties of ____ and _____

cell membrane molecule size lipid solubility small lipid soluble membrane proteins vesicles membrane and molecules

Function: Occluding Location: ___-____ Junctions Type: ____ function Membrane proteins: (2) Cytoskeleton fiber: __

cell-cell Tight Claudin, Occludin Actin

Receptor Physiology • A stimulus is a _____ detectable by the body. • •Stimuli exist in variety of energy forms or modalities, such as heat, light, sound, pressure and chemical changes. • •Afferent neurons have receptors at their ______ endings that respond to the stimuli in both the ____ and _____ environment

change external and internal

Mechanism of accommodation •The shape of the lens and its strength is regulated by the ____ ______ •The ciliary muscle is a circular ring of smooth muscle attached to the lens by ____ _____ •The ciliary muscle is controlled by the ____ -___ ____ •In the normal eye, the _____ _____ is relaxed and the lens is _____ for far vision. When the ciliary muscle contracts, the lens becomes more _____ and -____ for near vision

ciliary muscle suspensory ligaments. autonomic nervous system. ciliary muscle flat convex stronger

Gap Junctions Allow Small Molecules to Pass Directly from Cell to Cell •cell-cell "_______ _____", pass molecules smaller than _____ daltons •six connexin proteins make _______ —aligned with a neighboring cell • Gap junctions o Membrane of two neighboring cells o Pore and channels connect the cells Exchange varies types of materials Restriction in size

communication sites 1000 connexons

• Differences between tonicity and osmolarity - Osmolarity describes number of particles in solution, has units osmoles/liter; Tonicity is only a __________ term - Osmolarity can be used to compare any two _______ ; Tonicity always compares a ___ to a ____ • Osmolarity does not necessarily tell what happens to a cell placed in the solution. Tonicity by definition tells what happens to cell ____ .

comparative solutions solution cell volume

Homeostasis The body cells can live and function only when the internal environment, or extracellular fluid is _____ with their survival • Internal environment must in ____ in limits ______: Maintenance of the relatively stable internal environment (homeo-"the same"; stasis-"to stand or stay")

compatible capped Homeostasis

Two factors influence a cell's membrane potential: 1) the____ ______ of different ions 2) the ________ of the membrane to those ions. If the cell permeability to the ion changes, its' membrane potential changes.

concentration gradient permeability

FLUX ?? Rate of diffusion/surface area =(________) • Flux is defined as ______ rate per ___ ___ of the membrane. • Flux depends on the _____ _____ and ____ _____ of the molecule. Diffusion _____ Eliminates concentration gradients Until equilibrium, moves DOWN concentration and make concentrations equal

concentration gradient * membrane permeability diffusion surface area concentration gradient membrane permeability

Carrier proteins change _____ to move molecules • Much larger_____ or ____ with help of carriers o Most a proteins, work through confirmation of changes o Picture 22 Carrier proteins A carrier that moves more than one kind of molecule at one time is called ______ . • If they move in same direction- _____ • Opposite direction- ____

conformation , glucose or AA cotransporter symport antiport

5 Senses; Sight, hearing, taste, touch, smell • Sensory receptors also relay information that does not reach _____ •(3) The Senses •________ senses provide information form the body: touch, pressure, vibration, temperature, pain (nociception), proprioception, blood pressure, O2, CO2 •____ _____ receptors are concentrated in specific organs rather than being broadly distributed throughout the body: smell, vision, taste, hearing and equilibrium

consciousness pH, Pressure, temperature Somatic/visceral Special Senses

• Increase cholesterol—____ ______ permeability of membrane • Two properties •____ and ____ _____ Smaller and more lipid soluble the more easily they move across membrane • ______, _______ molecules, _____ _____ molecules (water, ethanol) o Can cross on their own x____ _____ molecules and _____ molecules o Can not cross of their own

decrease water Size and lipid solubility Gases, hydrophobic small polar small polar charged

Graded Potentials • •In a typical neuron graded potentials are generated in the ____ and ____ ____ in response to incoming signals. • If the graded potentials have sufficient magnitude by the time they spread to axon hillock, they will bring the membrane to the threshold and initiate an _____ at this triggering zone. • If potential change is below the threshold no AP will be generated and nothing will happen. • Further away from stimulus, amplitude ______ , then it reaches trigger zone and depolarized and the AP is generated down the axon • If when it reaches the ____ _____ the amplitude does not reach threshold, nothing will happen

dendrites and cell body AP decreases trigger zone

Cell-to-Cell: Events at the Synapse and Exocytosis *** SLIDE 58 • An action potential_____ the axon terminal. • The depolarization opens voltage-gated `-____ channels and Ca2+ enters the cell. • Calcium entry triggers______ of synaptic vesicle contents. • Neurotransmitter diffuses across the __ ____ and binds with receptors on the postsynaptic cell.—by exocytosis • Neurotransmitter binding initiates a_____ in the postsynaptic cell. o Receptor activation, then creating response o Usually involves opening or closing ion channels, and increase and decrease the_____

depolarizes Ca2+ exocytosis synaptic cleft response permeability

************************************ 22 Closed • Voltage-gated o AP generation o Open when the cell _____ Ligand-gated extracellular or Intracellular • ____ gated o Respond to Pressure, pressure increase, tension increases, allows sodium ion to pass Which molecule could NOT pass through an open ion channel based on size alone? • _________

depolarizes Mechanically Protein

Stages 1. Rising—______ 2. Falling- ______ 3. After- ______ a. Undershoot threshold 4. Then to ______ mV- RMP Graphs 39 • ______ —Open Na+ channels, less negative to +30mV o Then Na+ closes, at the same time K+ channels open • ______ -- open K+ channels, more negative, K+ leaves the cell o Falling phase of AP • Then normal RMP _____ mV, the K+ still open, close to close and open still go out and gets even more NEGATIVE—the after ______ then when the close, the membrane potential returns to the RMP which is -70mV.

depoliaton repolizarion hyperpolization -70 Depolization Repolization -70 hyperpolization

Dermatomal Map •The innervation arising from a single dorsal root ganglion and its spinal nerve is called a _______ . •Knowledge of dermatome arrangement is particularly important in defining the location of _______ •"___________ " is a general term that refers to back pain that radiates down the leg. The most common cause of sciatica is spinal disk herniation that impinges upon a spinal nerve, resulting in a dermatomal pattern to the pain. Clinical application: shingles • ______ - infection of sensory nerve by chicken pox virus (herpes zoster) Virus may lie dormant inside dorsal root ganglion neurons for many years • Virus replicates and leaves sensory nerve terminals damaging the ____

dermatome suspected spinal (and other) lesions. Sciatica Shingles dermatome

Diffusion can take place in an open system or across a partition that separates two systems •Substances that can pass through the lipid center of a membrane move by __________. •Diffusion directly across the phospholipid bilayer of the membrane is called _____ _____ Depends on properties of the ______ and _____ • Lipid bilayer is called SIMPLE DIFFUSION

diffusion simple diffusion. MEMBRANE AND MOLECULES

•The normal functioning of the basal ganglia involves a proper balance between the activity of direct and indirect pathways. •Basal ganglia activate the motor program stored in motor cortex circuits appropriate for the current task via the ____ _____ and inhibit competing motor programs via the ___ ____ •Voluntary movements are not initiated in the ___ ____ (they are initiated in the cortex); • Movement is initiate in the ____ ____ • Basal ganglia act as a____ that enables the_____ of appropriate motor programs in the motor control hierarchy

direct pathway indirect pathway. basal ganglia MOTOR CORTEX gate execution

The rate of diffusion is _____ proportional to the surface area of the membrane •Large surface area for diffusion: As lung tissue breaks down and destroyed in emphysema, the surface area available for diffusion of oxygen decreases=> less oxygen can move into the body

directly

Active transport moves molecules against their concentration gradient • Active transport creates a state of ______ • Make concentration difference even more pronounced • Requires ____ • Energy for active transport comes directly or indirectly from the high-energy _____ bond of ATP Active transport can be divided into two types: _____ and _____ •In primary active transport the energy to push molecules comes directly from the high-energy ________ bond of ATP.

disequilibrium energy phosphate primary (direct) and secondary (indirect) phosphate

Graded Potentials dissipate with distance • Degree of depolarization caused by the graded potential decreases with _____ from the origin: "ripples created by a stone tossed into a pond" • Further away from stimulus origin, the amplitude of the graded potential decreases

distance

When of the following charasitics of action potentials and/or graded potentials is correct Graded potentials dissipate with distance In order to signal a stronger stimulus, action potentials become • More ______ AP propagation • Once an AP is initiated no further triggering event is required to activate the rest of the nerve fiber. The impulse is _____ conducted throughout the neuron without further stimulation by one of two methods of propagation: o Will happen automatically

distance frequent automatically

Pharmacological Treatment of PD • Goal = Restore ______ receptor function • Several types of drugs: • • Levodopa L-DOPA • • Dopamine Receptor Agonists • • Monoamine Oxidase Inhibitors (MAOIs) • • Catechol-O-Methyltransferase (COMT) inhibitors • Current pharmacological therapies for PD do not prevent the continuous degeneration of nerve cells in the____ ____ and therefore are symptomatic.

dopamine subtantia nigra,

Inflammatory Pain •In a damaged tissue cells release chemical mediators creating socalled "inflammatory soup": bradykinin, prostaglandins, serotonin (5-HT), NGF, ATP, H+ • Components of the " inflammatory soup"actvate nociceptor neurons •Activation of the nociceptor neurons transmits afferent messages about painful stimuli to the spinal cord ___ _____ (and from there to the brain), and also initiates the process of neurogenic inflammation: release of polypeptide pro-inflammatory mediators • substance P and calcitonin gene related peptide (CGRP)) from the peripheral terminals of nociceptor neurons. • Also help inflammatory • They actively participate in the activation of an inflammatory response: ____ ______

dorsal horn - neurogenic inflammation

Cytoskeleton is essential for cellular movement • Highly _____ • Essential for _____ and _____ of the cell • The movement of lymphocytes (shown in red) within the lymph node of actin • Lymphocytes move because of the assembly and disassembly The lymphocytes move mainly as a result of the organized assembly and disassembly of ____ ____

dynamic movement and migration actin networks

The____ ___ ___ is a network of neurons in the walls of the digestive tract • Neuronal networks—its own integration center • ____ ____ " _____ is the functional unit of the nervous system • Cell body- ____ - contains a nucleus • ____- incoming information • _____ - outgoing information SLIDE 11 ****

enteric nervous system "mini break Neuron soma Dendrites Axon

******************************** 41 Distribution of epithelia in the body •____ _____ protects the internal environment of the body and covers all surfaces of the body, which are in contact with external environment Epithelial transport • Transcellular : • ______ : Passive but selective variable and regulated • epithelial cells are connected by - ____ ____ o need a bio cellular pathway o need to cross ___- membranes on their way

epithelial tissue Paracellular -Tight junction two

The body is in osmotic equilibrium • Water is able to move between cells and the extracellular fluid and distributes itself until water concentrations are _____ throughout the body • _______ is a form of diffusion specific to water: movement of water from a region of ___ solute concentration (i.e. _____ water) to a region of ____ solute concentration (i.e. ___ water) across a semi-permeable membrane High concentration of _____ to low concentration of water = salt or sugar LOW ______ concentration, HIGH ____ concentration o Osmosis—High to Low _____ concentration low to high ____ concentration Until EQUAL

equal Osmosis low high high low water solute solute WATER solute

Mitochondria • The sites of most ATP generation, "cell's powerhouse"; the number of mitochondria in particular cell depends on the cell's energy needs Mitochondria have their own unique DNA and can manufacture some of their own proteins; they are able to replicate themselves even if the cell is not undergoing cell division (e.g. ____ _____ cells that experience increased energy demands can have increased number of mitochondria).

exercising muscle

***************************************** ************************************ 73 Occluding Junctions (Tight Junctions): Epithelial Barrier Function and Cell Polarity Organization Lumen of intestine is outside the body - ___________ environment Major function of intestine of epithelial - keep lumen outside and keep things from entering • Outtake the nutrients from the lumen and bring it to other side ?? • Cells form tight junctions o Prevent passage by most molecules by ____ ____ o Also divide membrane into two different membranes ??? (2) • Allows the direction of transport across the ____ cells o Epithelial is a _______ epithelial cells o ONLY On the apical membrane of cell ?? 73 • Disorganization of intestinal body- IBD, chromes disease and ???

external cellular path Apical membrane Basal membrane epithelial cells polarized

Sympathetic Stimulation • Lens becomes _______ , weak, lens • ____ objects Parasympathetic Stimulation • _____ , long lens • ____ objects Control of pupillary size • Parasympathetic stimulation causes ____ muscles to contract o Bright light, sun light • Sympathetic stimulation causes ____ muscles to contract o Dim light

flattened Far Rounded Close circular radial

The beating of cilia and flagella creates x______ movement The wave-like motion of the ______ of a sperm cell. The cell was photographed with stroboscopic illumination at 400 flashes per second. Defective dynein arms cause problems with movement of cilia and flagella and result in ____ ____ and ______ _____ and _____ problems.

fluid flagellum male infertility respiratory tract and sinus

Single Twitch: muscle relaxes completely between stimuli • Single twitch does not represent a maximum tension that a muscle fiber can develop. The force generated by the contraction of the single muscle fiber can be increased by increasing the ____ at which APs stimulate the muscle fiber ______- : stimuli closer together do not allow the muscle to relax fully • Until reach maximum tension

frequency Summation

Measuring Membrane Potential Difference In living systems by convention, the ECF is designated as a ground and assigned a charge of 0 mV. Inside of the cell is negative, and the difference is 70mV RMP- ________ Artificial cell-impermeable to all ions • Both the cell and solution are electrically neutral and the system is in electrical equilibrium, but not chemical equilibrium: 4 ions in the system would diffuse down their concentration gradient if they were able to cross the membrane

-70mV

KEY POINTS • PD affects _____ % of the general population over the age of ____ . • Most cases of PD are most likely due to combination of____ and _____ factors. • Symptoms include muscle ____ , ____ _____ , _______ , impairment of ____ ____ • Characterized by severe loss of _____ ____ DA neurons and presence of ____ ____ • Therapy is only ______ and includes _______ (with carbidopa), DA receptor agonists, ____ ______ Inhibitors (MAOIs), Catechol-OMethyltransferase (COMT) inhibitors.

1-2 65 genetic and environmental rigidity resting tremor bradykinesia postural balance. substantia nigra (SN) Lewy bodies. symptomatic levodopa Monoamine Oxidase

Human Cells Come in Many Different Shapes and Sizes o Blood cells o Muscle cells o Nerve Cells o Osteocytes o There are more than ____cell types Various cell types in a multicellular organism differ dramatically in ______ and ______ • Structure difference are related to the _____of the cell • ______ —receive inputs from different cells and sends the output to many different places • _______—responsible for immune response o Most active, need to leave blood stream and to site of injury or inflammation o Need to crawl between o Very small • But have the same ____ but the express different cells

260 structure and function function Neuron Lymphocyte GENO

Na+-K+-ATPase (-potassium pump) ** slide 27 • Works through confirmation of changes Figure 5-14, steps 1-5 1. ___ ______ from ICF bind o ATP ----> ADP 2. ______ is ________ with Pi from ATP o Protein changes ______ 3. _________ released into ECF 4. ______ from ECF bind o Protein changes conformation • 2 K+ released into _____

3 Na+ ATPase phosphorylated conformation 3 Na+ 2 K+ ICF

Small Motor units produce precise movements •In muscles used for fine motor actions, such as the muscles that move the eyes, a motor unit contains only ~ __---__ muscle fibers. This arrangement allows fine gradations of movement. •In muscles used for gross motor actions such as standing or walking, each motor unit may contain hundreds or thousands of muscle fibers. •The _____ muscle in the calf of the leg has ~ 2000 muscle fibers in each motor unit.

3-5 gastrocnemius

ICF- ____% of body weight ECF • interstitial Fluid (IF) o _____ % body weight • Plasma o ____% body weight •Interstitial fluid can move into ______ _____ and helps to maintain adequate _____ _____ in a patient who is hemorrhaging •The patient must lose about ____ L of ECF, before the volume of the plasma is decreased by ___ L.

40: IntraCELLULAR fluid 16 4 intravascular space blood volume 5 1

• Myelinated fibers conduct impulses about ____ times faster than unmyelinated fibers of comparable size.

50

Distribution of water volume in the three body fluid compartments ICF- most of the water in your body about ____ % ECF- ____ % of ECF Plasma • Interatrial Fluid (____ % of ECF) percent of total body water in ECF ____

60-65% 25 75 30%

Parasympathetic • SLUD6 • Salivation • • Lacrimation • Urination • D x 6 • 1. Defecation • 2. Digestion • 3. Decreased HR • 4. Decreased diameter of airways (constriction) • 5. Decreased diameter of pupil = constriction (lens- near vision) • 6. Dilation of erectile tissues (erection) Only Sypathmetic____ _____ and ??? Both against each other- salvary and sexual function

: smooth muscles

Sliding Filament Model •In 1954 Andrew Huxley and Rolf Niedergerke discovered that length of _______ remains constant during contraction. • Length of _____ filament does not change during muscle contraction • Length of _____ and _____ filament do not change but they slide along each other in an ____ depended process

A band thick thick and thin ATP

Neurotransmitters Slide 61** Excitatory/ Inhibitory •(3) Generally Excitatory •_____ * major excitatory NT in brain •______ Generally Inhibitory •_____ * major inhibitory NT in brain •_____ * major inhibitory NT in spinal cord • Serotonin • Histamine • Substance P • Endorphin • Enkephalin

A cetylcholine, Norepinephrine, Dopamine Glutamate GABA Aspartate Glycine

Nicotinic cholinergic receptor • Nicotinic- Ionotropic receptors • Transmembrane integral proteions • No ___- bound: channel closed •___ ach molecules bound: Channel open Excitation-Contraction Coupling 1. Somatic Motor neuron releases ____ at NM junction 2. Net entry of _____ through ACH receptor- channel initiates a ______ -____ 3. Action potential in ___ ____ alters conformation of DHP receptor 4. DNP receptor channels in sarcoplasmic reticulum and ____ enters cytoplasm 5. Ca2+ binds to ______ , allowing actin-myosin binding 6. Myosin heads execute ____ -___ 7. Actin Filament slides forward ______ of sarcomere

ACH Two Ach Ach Na+ muscle AP t-tubule Ca+ troponin power stroke center

Most internal organs are under ____ _______ our autonmonc branch is excitatory and the other branch is inhibitory SNS—____ amount _____ saliva Para—____ amount of _____ salavia Sympathetic—______ Sweat glands—_____ only Smooth muscle blood vessels—_____ • Does constricts and dilates Sympathetic Division: Time to flee • ____ : the branchi relax and more air can flow into the lungs respiratory rate increases • ___ ____ : the bood flow in the muscles increase and they contract • _____ : Produces sugar that is released into the blood stream ____ ____ release fatty acids into the blood steam •_____ and ______ The blood flow to the digestive system is decreased • ____ : HR and contractility increase • _____ : The pupils expand. The person get tunnel vision

ANTAGONISTC CONTROL: small thick large thin ejaculation sympathetic sympathetic Lungs Muscle Tissue Liver • Fat calls: Stomach and intestine: Heart Eye

• •Because the only way the afferent neurons can transmit information to the CNS about these stimuli is via ____ _______ receptors must convert these forms of energy into ___ ________. This energy conversion process is known as ___ ______ o Receptors must convert stimuli into_____ _____ called a sensory transduction • The ______ the stimulus, the greater the action potential • Some receptors have the ability to diminish the extent of their depolarization despite sustained stimulus strength, a phenomenon known as ______ .

AP propagation, electrical signals (APs). sensory transduction. electrical signals (Aps) higher adaptation

• Do not use ATP hydrolysis • Uses another molecules o Using energy of sodium ions, to push glucose into cell against glucose concentration gradient. o Use Sodium concentration gradient, and that is establish by _____ o Do use energy from ATP hydrolysis

ATP

Skeletal muscle contraction requires steady supply of ____ Muscle at rest ATP from metabolism + creatine with creatine kinase _____ + _______ Working Muscle Phosphocreatine + ADP creaatine kinase ____ and _____ needed for • Myosine ATPase : _______ • Ca2+ ATPase : ______ • Na+ K+ ATPase: ______ ions that cross cell membrane during action potential to their original compartments

ATP ADP + Phosphocreatine creatine + ATP contraction relaxation restores

Secondary Active Transport • Do not use ____ ___ directly • One molecule ____ the concentration gradient to move another molecular ______ the gradient • Most Secondary are ____ dependent transporters

ATP hydrolysis down against sodium

The patient suffers from muscle Dystrophy, Will admisisteraton of acetylcholinesterase inhibitor, such as neostigmine increase strength of muscle contraction in this patient • No. only increase ___ in synaptic cleft o Muscule dys. Is within the muscle self, not with innervation

Ach

Organophosphate poisoning treatment • Atropine reduces the symptoms by blocking the action of _____ at muscarinic AchRs. • ______ {obidoxime, pralidoxime (PAM) and _____ (HI-6)} are used to restore acetylcholinesterase functionality - "cholinesterase regenerators". • Inhibition, desinhibition, and aging of ACHE. X is leaving the group

Ach Oximes asoxime

****************************************** Summary of Muscle Contraction 1. Events at Neuromuscular junction: convert ____- signal from motor neuron into _____- signal in muscle fiber 2. ______________ : process in which muscle APs initiate Ca2+ signals that in turn activate a contraction-relaxation cycle 3. Ca2+ signal 4. ____-______ cycle 5. Muscle Twitch and Sliding Filament theory a_____ ___ : one contraction relaxation cycle in intact muscle b. Described by the sliding filament theory

Ach electrical Excitation-contraction coupling Contraction-relaxation . Muscle Twitch

Pain classification _____ —limited period of time • Tissue injury or repair • Post- operative • flare _______ —long periods of time • Nociceptive - inflammable fain o Osteoarthritis o Rheumatoid arthritis • Neuropathic Pain o____________ Post-stroke, MS, Spinal cord injury, migraine, HIV related pain ___________ Post- Herpetic neuralgia Diabetic neuropathy o _______ Internal Organ __________ Inflammatory bowel syndrome o Mixed Low back Cancer Fibromyalgia

Acute Chronic pain Central (CNS) o Peripheral (PNS) Visceral Pancreatitis

*************************** ______ • Stimulate NE release: Edhedrine and amphetamine—indirect agonists o Both adrenergic and dopaarmc • Prevents NE uptake: Cocaine What is the function of acetylcholnsterase • It breaks down NT acetylcholne into choline Neostigmin is an ACETYLOOCHOLINESERASE inhibitor • Neostigmine acts as indirect agonist of cholinergic receptors SLIDE 31 • Cholinergic receptor—inotropic ion • Mucarinic receptors are_____

Adrengic

Functional PNS can be divided into: - Sensory Division • • _____ division o - Conducts impulses from _____ to the ____ o - _____ the CNS of the state of the body interior and exterior o Sensory input to CNS—reports about ____ and _____ environment • - Motor Division • _____ division o - Conducts impulses from ____ to ____ o ___________ : skeletal muscle o -___________ - smooth & cardiac muscle, glands o From the CNS to periphery

Afferent receptors CNS Informs external and internal Efferent CNS to effectors - Voluntary (somatic) - Involuntary (autonomic)

A chemical that activates the receptor to produce a biological response is called • _____ Autonomic agonists and antagonists are important tools in research in medicine • Direct agonists and antagonists combine with target receptor to ___ or ____ receptor action. • ______ agonists and antagonists act by altering secretion, reuptake or degradation of neurotransmitters. o Do not bind to receptor itself but still alters o Ex. Nicotine—direct o Cocaine- indirect Which of the following is an example of indirect agonist of adrenergic receptors •______

Agonist mimic or block Indirect Amphetamines

_____ ____ ____ - skeletal muscle movement • Called the lower motor neurons Upper Motor neuron • Motor cortex neurons Lower and upper motor neurons • Motor neurons in the spinal cord are referred to as ___- ____ ____ All motor system neurons higher in the hierarchy are referred to as ___ ____ _____ • Differences in the_____ that result from damage at different levels of motor control allow the clinician to localize where in the hierarchy the damage is likely to be. • Axons directly terminate on the______ • Innervates the skeletal muscle • When____ lesion—flaccid, paralysis, decrease muscle tone, decrease reflex response, or no reflex, muscular atrophy

Alpha Motor Neurons lower motor neurons. upper motor neurons. symptoms muscle LMN

Types of Neurons Multipolar- multiple •____ _____ _____—innervate skeletal muscles Unipolar- one extension • example Bipolar- two extenson • ____

Alpha motor neuron Sensory receptors to CNS Retina

_____________ where the loss of hippocampal and cortical neurons leads to impairment of memory and cognitive ability Most common o -____________ , where muscular weakness results from the degeneration of spinal, bulbar, and cortical motor neurons o •Currently available therapies for neurodegenerative disorders ____ the disease symptoms but do not alter the underlying neurodegenerative process

Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS) alleviate

•_______ increases levels of DA and NE primarily by blocking their reuptake or promoting their release. o Noeph and dopamine o Presynaptic relreases dopamine into synaptic cleft and causes the reuptake of Noeph, NT accumulates in synaptic cleft and help us activate other receptors o Signal is_____ o With presence of amphetamine—______ is not packaged and reverses the function of dopamine transported Then it starts to release dopamine into synaptic cleft

Amphetamine enhanced dopamine

___ _____ ___- • Neurodegenerative disease • Progressive loss of both upper and lower neurons • Muscle lose their normal innervation, • Serve muscle atrophied muscle Muscle Diseases: The Muscular Dystrophies • Diseases that cause progressive weakness of skeletal muscle • The ______ of the affected muscles is preserved • Associated with genetic defects that involve ______ expressed exclusively in muscle • Innervation is no damaged, it the ___- ____ themselves

Amyotrophic lateral sclerosis innervation proteins muscle fibers

The largest and most abdunant of the CNS glial cells, help forms the blood brain barrier • ____________ Which of the following is the route of administration that is most likely to get the high-test concentration of a drug in the brain __________________ Which of the following drugs is most likely to diffuse across the blood brain barrier ______________________ Glial cells that are phagocytic within the CNS are • ____________

Astrocytes • ICV, intracerebral ventricle injection • Molecular mass 5DA, high lipid solubility Microglia

Neuroglia of CNS •______ (astro- means "star") -The most abundant glial cells, the main "glue" of CNS, hold neurons together in proper __ ____ -Important in the _____ of brain injuries and in ___ ____ formation -Play a role in neurotransmitter activity: take up ____ and _____ (inhibitory) neurotransmitters bringing their actions to a halt * • can participate in neuro transmission-- -Regulate composition of the brain ECF by taking up excess_____ after high action potential activity (recall that K+ leaves the cells during the fall phase of action potential) -Induce anatomical and functional changes of ___ ____ ___in the brain that are responsible for establishing the _____________ • between the blood and brain

Astrocytes spatial relationship repair neural scar glutamate and GABA K+ small blood vessels blood-brain barrier (BBB)

________ recruitment of motor units • Helps to avoid fatigue • Different motor units take turns maintaining the muscle tension • The ______ of active motor units allows some of motor units to rest between contractions • Works only for ______ contractions Recruitment of additional motor units in skeletal muscle will result in • ______ muscle force

Asynchronous alternation submaximal Increased

Clinical Importance of Cholesterol ______ is the formation of cholesterol plaque due to its accumulation in the vascular endothelium. Growth of the plaque results in _______ of arteries and _________ Atherosclerosis of the coronary arteries is the common cause of _____ ______

Atherosclerosis stenosis (narrowing) ischemia (insufficiency in blood supply) myocardial infarction.

Muscarinic receptor antagonists • _____ is nonselective muscarinic receptor competitive antagonist; relatively lipid-soluble and is well distributed into the CNS and other organs. The duration of action of normal doses is 4-8 h except in the eye, where effects last for 72 h or longer. Organophosphate poisoning • _________ insecticides and nerve gases (tabun, sarin, soman) inhibit AchE by phosphorylating a serine hydroxyl group (Ser203 in HuAChE), which is directly responsible for the hydrolysis of Ach. Organophosphate poisoning Symptoms: • ______ - salivation, lacrimation, urination, diaphoresis(excessive sweatin), gastrointestinal motility, emesis • _______ - diarrhea, urination, miosis, bradycardia, bronchoconstriction, excitation (muscle fasciculations and CNS), lacrimation, salivation, sweating

Atropine Organophosphate SLUDGE DUMBBELSS

********************************* 42 Two membranes of Epithelia Apical membrane- secretion ? ____ ______ - absorption _____ cells of transporting epithelia Polarized epithelia have different ____ ____ on apical and basolateral membranes. This allows ______ directional transport across the epithelium. Transport from the lumen to ECF - ______. Transport from ECF to lumen -_____ . • Increased epithelial permeability is a well-accepted consequence of ____ ____(e.g. leaky intestinal barrier is considered an important contributor to the pathophysiology of ____________ which includes both _____ disease and ___ _____ .

Basolateral membrane Polarized transport proteins selective absorption secretion mucosal inflammation inflammatory bowel disease (IBD), Crohn's Ulcerative Colitis

Divisions of the Nervous System Anatomic Central nervous system (CNS) • _____ and ____ ____ Peripheral nervous system (PNS) Peripheral nerves: -____ Spinal nerves • »Carry info to and from the spinal cord -____ Cranial nerves • »Carry info to and from the brain Divisions of the Nervous System

Brain and spinal cord 31 12

Microtubules form ___________ • ________ direct DNA movement during cell division • ______ along with ______ constitute the core of cilia and flagella-highly specialized and efficient motility structures. • ______ are longer than ____ (sperm movement). • _______ sweep fluids past stationary cells in the lining of ______ and tubes of _____ _____ • Both flagella and cilia have a _______arrangement of microtubules. • ______ "arms" attached to the microtubules serve as the molecular motors. ??? uses ATP 54 Ciliis is where ? (3)

CENTRIOLES Centrioles Microtubules dynein Flagella cilia Cilia trachea female oviduct. 9 + 2 Dynein epithelial cells, respiratory, and female reproduction tract

KEY POINTS • The nervous system consists of the _____ , which includes the brain and spinal cord, and the PNS, which includes ______ carrying information to (afferent division) and from (efferent division) of the CNS. • Three functional classes of neurons-afferent neurons, efferent neurons and interneurons-compose the ______ cells of the nervous system. • _____ are responsible for integrating afferent information and formulating an efferent response, as well as for all ____ -____ _____associated with "mind". •_____- ______ physically, metabolically and functionally support the neurons. • The brain is provided with several ____ _____ which is important because neurons ____ divide and replace damaged cells. • CNS is wrapped in three layers of protective membranes called -__________ . • ______ flows within and around the brain to cushion it against mechanical damage. • Protection against chemical injury is conferred by a _________ (drug design problem).

CNS fibers excitable Interneurons higher mental functions Glial cells protective devices, can't meninges CSF BBB

•Clear fluid fills the ventricles, central canal and the subarachnoid space; CNS "floats" in _____ •CSF total volume is ________ml, replaced entirely ~ ___ X/day through the ongoing processes of formation, circulation, and absorption into venous blood in the ____ _____(arachnoid villi) •Removal of even few ml of CSF during a spinal tap may produce severe _____ CSF -____ _____ fluid - Removal can produce series ____

CSF 125-150 3 arachnoid granulation headaches Shock absorption headaches

Cellular actions of opioid receptors slide 44* •Opioids produce two well established direct G-protein coupled actions in neurons: *1)they close voltage-gated ____ channels on presynaptic nerve terminals and thereby reduce neurotransmitter release 2) they hyperpolarize and thus inhibit postsynaptic neurons by opening K+ channel -- uses _____ Use Glutamates and substance P—binds to NK1 and NMDA receptors K+ leaves—hyperpolizes the membrane—decrease ability to generate an AP by secondary neuron Information about painful stimulus never reaches brain, = ___ _____

Ca2+ exycytosis pain relief

To end the contraction the SR pumps Ca2+ back into its lumen using ___________ free cytosolic Ca2+ decreases Ca2_ releases from _______ tropomyosin blockage of actin binding site is _____ contraction end and muscle fiber relaxes Electrical and mechanical events in muscle contraction ____ _______ -single contraction-relaxation cycle in a skeletal muscle fiber •During relaxation, ______ elements of the muscle return the sarcomeres to their resting length

Ca2+--ATPase , troponin restored •Muscle twitch elastic

Cell Adhesion •______ "glue" and keep cells together • Attach cell to cell •_______ provide connection between the cytoskeleton and extracellular matrix • Cell cite to skeleton • _____ to elements of the _____ The Cell is composed of - 47 • 1. _________ • 2. ____________ o _______ ______ - have membranes Mitochondria Endoplasmic Reticulum Golgi Complex Lysosomes Peroxisomes o ______ —no membrane Lipid droplets Glycogen Granules Ribosomes Vaults Proteasomes Cytoskeleton Centrioles Centrosomes Cilia Flagella * __________ 3. _____ _____

Cadherins Integrins Membrane ECM Nucleus Cytoplasm Membranous Organelles Inclusions cytosol Cell Membrane

The Golgi complex was first described by ____ ____in ____ . • The Golgi complex receives proteins made on rER, _____ them, ____ them, and _____ them into vesicles • "post office"

Camillo Golgi 1898 modifies stores packages

•-_______ is FDA approved for the temporary relief of minor aches and pains associated with backache, strains, and arthritis and is used for off-label treatment of postherpetic neuralgia and diabetic neuropathy. • Primary afferent neurons—too much ?? • MINOR aches, if used too much, desensitization • Nature Reviews Drug Discovery 8, 55-68, January 2009 Menthol—acts on different type of channels • Stimlulates and then desynthesizes TRPMS

Capsaicin

________ •Chronic exposure to capsaicin first stimulates and then desensitizes _______ channel to capsaicin and other noxious stimuli; it might also cause degeneration of epidermal nerve fibers, thereby producing diminished sensation of ______ (hypalgesia).

Capsaicin TRPV1 pain

Interdependent relationship of cells, body systems and homeostasis • Homeostasis is essential for every cell in the body o _____ make up the body systems o Body systems maintain _____

Cells homeostasis

Types of Fatigue ____ _____ : Psychological effects, protective reflexes • Decrease ___ release • Decrease _____ activation ______ ______Change in muscle membrane potential o SR Ca2+ leak o Decrease ____ release o Decrease Ca2+ _____- interaction o Depletion theores: Pcr, ATP, glycogen o Accumation theories H+, Pi and lactate

Central Fatigue NT receptor Peripheral Fatigue Ca2_ troponin

Functions of Integral Proteins • _____ - regulated pores that control flux of ions and water in or out of cells o Channel—ONE PROTEIN SUBUNIT OF CHANNEL—Channel o Named after the ___ that they allow to pass o Move ____ _____ or ______ molecules •______ or ______ proteins - transport of glucose, amino acids and other substances which can't diffuse across the phospholipid bilayer • Receptors - reception of signals by binding _____ ___ or _____ neurotransmitters, drugs, etc.) o ???? o Facilitate the process called ____ _____ ?? o

Channels ion small ions or water Transporters or carrier external chemicals or ligands ( signal transaction

• Highest level in hierarchy •_____ movements • Primary- no______ movement _____ purposeful/complex voluntary movement

Complex purposeful • Premotor cortex-

miosis = miotics (drug name) • _______ of pupil • Stimulate parasympathetic and ______ muscles • _______________- : minic actions of the parasympathetic nervous system mydriasis = mydriatics • We have _____ parasympatheric o ________ • Or stimulate -_____ branch o ____ muscles o Sympathomimetics

Constriction circular Parasympathomimetics INHBIT Parasympatholytics sympathetic Radial

ANS control of the eye Parasympathetic • ______ pupil (contraction of ____ muscles) • Contracts ______ muscle (thickens the lens for near vision = _____ ) Sympathetic • ______ pupil (contraction of radial muscles) • _____ ciliary muscle (flattens the lens for ______ vision)

Constricts circular ciliary accommodation Dilates Relaxes distance

Neuromuscular Blocking Drugs _______ is an example of a muscle relaxant that blocks the nicotinic cholinergic (nAChR). The main toxin of curare, known as tubocurarine, occupies the same position on the receptor as ACh with an equal or greater affinity, but elicits no response,making itacompetitive antagonist. • The toxic effects of batrachotoxin (BTX) are caused by sustained, irreversible opening of voltage-gated ____ ______ of nerve and muscle. • Channel is constantly open—can't relax

Curare sodium channels

Graph goes up means a _____ in membrane potential - less negative,, the difference decreases •In most cases membrane potential changes in response to movement of (4) • Most membranes are permeability to _____ • By 40 times more • Positively charged ion INSIDE the cell _______ • Low concentration of ____ in the cell

DECREASE K+, Na+, Ca2+ or Cl-. K+ - K+ CA+

Open the membrane to Na+ ions • _____ • Move into the cell Open the membrane to Cl- • _______ • Increase the cell • More x_____ • Down the concentration gradient Open to CA+ • _____

DEPOLARIZATON HYPERpolization negative DEPOLIZATON

Mitochondria have their own unique ____ and can manufacture some of their own ____ ; they are able to ____ _____ even if the cell is not undergoing cell division (e.g. exercising muscle cells that experience increased energy demands can have increased number of mitochondria). • The innermost compartment - _____ • They have their own _____ o Make their own _____ • They can ____ even if cell does not go under division

DNA proteins replicate themselves Matrix DNA proteins replicate

Sodium Equilibrium Potential The concentration gradient moving Na+ inside the cell (150 mM outside and 15 mM inside) is exactly opposed by positive membrane potential ENa= + 60 mV • Na+ move into cell _____ their concentration gradient • More _____ charge outside cell o Electrical Gradient Tries to more K+ outside cell RMP: K+ is -90mV RMP; NA+ is +60mV

DOWN NEGATIVE

Graph— Decrease in membrane potential—less negative is called _______ Increase in membrane potential—more negative- _________ Increase in negative—______ • Increase of the cell becomes even more negative, the difference INCREASES

Depolarization repolarization HYPERpolarization

Function: Anchoring Location: cell- cell junction Type: ________ Membrane proteins: _____ Cytoskeleton fiber: _____ _____

Desmosome Cadherin Intermediate filaments

Physiological Effects of the ANS Sympathetic • _____ pupil (lens - _____ vision) • _____ saliva • ______ heart rate & contractility • Vaso_______ • -____ bronchi • Stimulates -_____ production & lipolysis • _____ GI activity • Inhibits ______ • _____

Dilates distance Viscous Increased constriction Dilates glucose Inhibits urination Ejaculation

White matter consists of defined nerve tracts which are arranged in columns: •_____ columns carry sensory information - ascending information • _____ or _____ columns carry both sensory and motor information o Both, ascending and descending information ____ _____ —site of protein synthesis—Rough ER- spinal cord gray matter

Dorsal Ventral and lateral Nissle bodies

__________________________________ sensory pathway conveys fine touch, vibration, proprioception • ___ neurons that synapse • 1. Afferent sensory neuron o AP are generated and propagated long axon o Go to medulla of the brain stem, then makes synapse with second neuron of path • 2. Have body on _____ and go the ____ • _______ —relay and processing station before it gets to the cortex, only exception is olfactory information • It is a cross pathway--- at the _____ • Any damage below the medulla—cause loss of touch ect. On the ______ side • Above medulla—loss of sensation of touch on the _______ side • Crosses at the medulla ** book

Dorsal column-medial lemniscus (DCML) 3 medulla thalamus Thalamus medulla ISPILATERL CONTRALATERAL

Cortical control of motor functions The motor cortex comprises three different areas of the ____ ____ , immediately anterior to the central sulcus: ___ ____ ____ , the_______ , and the ____________ Primary motor cortex • •Movements can be stimulated by applying a very weak_____ _ currents • Detailed ___ ____: destruction of cortex in this area produces specific movement deficits • Deficit will happen at the______ of the body o Not_____ movements • Although the general organization pattern of somatotopic map of motor cortex is similar in all people, the precise distribution is unique for each individual • Neuronal output can be traced directly to the spinal motor neurons and produces movements in the_______ side of the body

frontal primary motor cortex premotorcortex supplementary motor area electrical somatotopic map; opposite fine contralateral

Physiology is the study of the normal _____ of a living organism and its component parts, including all its chemical and physical processes. PHYSIOLOGY Study of ____ ____

functioning body function

Autonomic Control Centers in the Brain * A ______ is a cluster of nerve cell bodies that lie outside the CNS. The equivalent in CNS is ______ . 1) Pathway point of origin in CNS 2) Location of autonomic ganglia Autonmonic pathways consist of two neurons that synapse in an autonmonic ganglion • CNS Preganglionicautonomic Ganglion Postganglionic Neuron Target Tissue

ganglion nucleus

The open or closed state of the channel is determined by regions of the protein molecule that act like swinging "____ " • Channels can be classified according to whether their gates are usually open or usually closed: • ____ _____ spend most of their time with their gate open, allowing ions move back and forth across the membrane without regulation. ____ _____ spend most of their time in a closed state, which allows those channels to regulate movements of ions through them

gates -Open channels • -Gated channels

Hierarchical Organization: • • The higher-order areas concern themselves with more____ tasks regarding action, such as___ when to act,______ an appropriate sequence of actions, and_____ the activity of many limbs. • • Low-level tasks, such as programming the_____ of individual muscles, are performed by the lower levels of the hierarchy. • The motor system have higher areas and lower area o Higher order— ? o Low- ____ and ___ ____ of muscles

global deciding devising coordinating force speed and contraction strength

************************************* 25 Facilitated diffusion of glucose into cells • Conversion of imported glucose into _______________ keeps intracellular glucose concentrations low so that diffusion never reaches the equilibrium. • Facilitated diffusion- uses a ___ _____ o But STILL _____ THE CONCENTRATON GRADIENT, NO ENERGY NEEDED • Simple diffusion ?? • Conversion ??

glucose 6phosphate (G-6-P) protein carrier DOWN

Stretch reflex • Physiological function of the stretch reflex is to resist_____ . When a load is placed on the muscle, it is stretched, which results in ___ _____ of the muscle to take up the load. Withdrawal Reflex • Withdrawal reflex can be_____ overridden

gravity reflex contraction voluntary

In the sliding filament mechanism cross bridges are • Mysosin _____ that bind active sites on a thin filament As ATP binds to myosin head at the beginning of a muscle contraction cycle • Myosin head _____ from actin ____- and ______ - Sympathetic - dilation • Dilated Is HR slower or fast than average in this patient (sympathetic) • ______ Is blood pressure likely to be lower or higher in this patient? • _____

heads detaches Epinephrine, norepinephrine Faster Higher

Endocrine system: • target cells are usually anatomically _____ dispersed ("wireless" system) • chemical messengers (______ ) usually diffuse ______ the body (long distance, carried by the blood) • acts ______ (minutes to hours) for a long period of time (minutes, hours, days)

hormones throughout slowly

Cerebrospinal fluid (CSF) MRI showing pulsation of CSF • Imbalance between formation, circulation and absorption of CSF can cause accumulation of excess of CSF, _______________ ("water in the brain") • Increases _____ ____ lead to damage •The resulting increase in CSF pressure can lead to ____ ____ and mental retardation if untreated • Treatment consists of surgically shunting the excess of CSF to ____ elsewhere in the body

hydrocephalus intracranial pressure, brain damage veins

Local injection of small doses of botulinum toxin A (Botox) is effective in the treatment of conditions characterized by muscle ________ : cervical dystonia, blepharospasm, strabismus, urinary incontinence. Also used to prevent headaches in adults with chronic migraine, treat the symptoms of severe underarm sweating and reduce the facial wrinkles

hyperactivity

Cerebellar disease •__________ is the inability to perform rapidly alternating opposite movements such as repeated pronation and supination of the hands •_____ _____ is absent at rest and initiated during voluntary movement toward the target •_____ _____ abuse can lead to cerebellar degeneration, most profoundly seen in vermis, causing patients to have gait ataxia

Dysdiadochokinesia Intention tremor Chronic alcohol

Most cells are in direct contact with • __________ o Outside cell but inside body o Absorb _____ from external environment • Levels of Organization o (9)

ECF nutrients Atom, molecule, macromolecule, organelle, cell, tissue, organ, organ system, organism

There are four primary tissue types in the human body (4) All organs are composed of these tissues

EPITHELIUM CONNECTIVE TISSUE MUSCLE TISSUE NERVE TISSUE

The human body has 3 types of muscle tissue: Skeletal Muscle • •_____ cells; long • •______ peripheral nuclei • •Visible ____ • •Voluntary Cardiac Muscle • •______ cells • •Single central _____ o One nucleus per cell • •Visible _____ • •Involuntary Smooth Muscle • •_____ shaped cells • •Single central _____ • •____ visible striations • •Involuntary

Elongated Multiple striations Branching nucleus striations Spindle nucleus No

_____ _____ is a network of interconnected membrane tubes that are a continuation of the outer membrane surrounding the nucleus • Smooth ER-synthesis of ____ ____ and ____ •Rough ER (rER)-_____ synthesis ?? • Proteins are assembled on ribosomes and then are inserted into the ____ _____ where they undergo chemical modification. • Ribosomes are attached to _____ side of rough ER

Endoplasmic Reticulum fatty acids, steroids and lipids. protein synthesis. rER lumen, cytosolic

Neuroglia of CNS • _____ _____ Line the internal cavities of the CNS: brain ventricles and spinal cord central canal • - Help form choroid plexuses that secrete ___________ • - Beating of ____ contributes to the flow of CFS throughout the ventricles o Cilia—flow of the CSF • -_____ _____ ____??? o specialized cells, differentiate into functional neurons o Ex. After tissue injury Cilia project to ____ Ependymal Cells lining the spinal cord central canal •It is thought that some neural stem cells remain unspecialized among the ependymal cells and in subependymal layer, and can differentiate into neurons in response to specific _____ mechanisms.

Ependymal Cells - Cerebrospinal Fluid (CSF) cilia Neural stem cells CSF signaling

• Four Primary Tissue types o _____ ______ lines the surfaces in the body o _____ _____ is made up of fibers that contract o _____ ______ consists of cells with projections that transmit electrical signals o _____ _____ Loose CT acts as padding under skin and elsewhere _____ and _____ are CT made up of cells in a hard or stiff extracellular matrix __________is a connective tissue made up of cells in a liquid matrix

Epithelial Tissue Muscle tissue Nervous tissue Connective tissue Bone and Cartilage Blood

Nernst equation - allows calculation of _______ ______ for any ion Eion (the membrane potential that exactly opposes the concentration gradient of ion) 61 = 2.303 RT/F at 37 *C R= the gas constant , F= Faraday constant Z= valence, the electrical charge of the ion [ ion ] = ion concentrations outside and inside of cell Eion is measured in millivolts, mV • if the membrane were freely permeable only to K+ membrane potential would be equal to the K+ equilibrium potential EK+

Equilibrium potential

Carrier Mediated Transport • Majority of biological molecules are not lipophilic => cannot use simple diffusion • Two forms of carrier mediated transport 1.______ _____ -passive, transports down gradient, requires carrier protein a. Similar to simple diffusion b. No _____ c. ____ to ____- concentration d. Help with membrane ?? 2. _____ _______ -requires energy, transports against gradient, requires carrier protein a. Against b___ to ____ concentration

Facilitated diffusion energy High to low Active transport . LOW to HIGH

Locations and Possible Causes of Muscle Fatigue ______ - reversible condition in which muscle is no longer able to generate or sustain the expected power output • Most fatigue from E-C failure is not ______ in normal indviduals • Extended sub-maximal exertion o Depletion of ______ stores may affect Ca2+ release from SR o ATP is not liming factor • Short- duration maximal exertion o Increase _____ decrease release of Pi from _____ and altered power stroke o Decrease ____ release • Maximal exercise o ____ imbalances o Increase ____- ECF o Altered Vm

Fatigue neuronal glycogen Pi myosin Ca2+ Ion K+

Function: Anchoring Location: cell-matrix junction Type:___________ Membrane proteins: _______ Cytoskeleton fiber: _____ Matrix Protein: ________ and other proteins

Focal adhesion Integrin Actin Fibronectin

Sensory receptors of the skin • Slide 18 •_____________ respond to painful stimuli, temperature, itch, joint movement or proprioception ______ : detect light touch and superficial pressure • ___ ____ receptor: detects light touch applied to skin ____ _____ : touch involved in two point discrimination (previous slide) • _____ ____ _____ : detects continuous touch or pressure •______ ______ detects deep pressure, vibration and proprioception

Free nerve endings: • Merkel's Disks Hair Follicle • Meissner's Corpuscles Ruffini's end organ Pacinian corpuscle:

Dopamine Synthesis, Metabolism, and Receptors • DA receptors are ____________ receptors (GPCRs) • Synthesize from Tyrosine hydroxdylase Dihydroxy-phenylalanine (DOPA) Dopamine • Divided into different groups depending • Turned off from a reuptake

G protein-coupled

•_____ is the major inhibitory mediator in the brain • 2 main groups o GABA A ______ receptors GABA channels Increases permeability to____ - ions—______ IPSP o GABA B ______ 7-transmembrane G protein Increases permeability to ____ and decrease permeability of ____ Hyperpolarization IPSP

GABA Ionotropic Cl- hyperpolarization Metabotropic K+ Ca+

• LIVING CELL RESTING MEMBRANE POTENTIAL o Permeability of several ions—you need to use the ____ not the nest equaton o ____ ____ AND ___ ____ Y OF EACH ION - contribute of the RMP Diffusing and electric forces moving K+ in and out—equilibrium—no net movement of K+ At rest, the interior of the cell is ____ . charged compared to the exterior, this negative charge is due to mainly ___________

GHK CONCENTRATION GRADIENT AND MEMBRANE PERMEABILIy neg • __________ - negative charged proteins, NET NEGATIVE CHARGE

Opioids • The opioid system of the brain consists of several endogenous opioid peptides: endorphins, enkephalins, and dynorphins. • Opioid receptors are ________ . • Most of the commercially available opioid analgesics act at the ___________ 4 major classes • Dynorphins, Endomorphins, B-Endophin, Enkephalins • Have 7G protein receptors

GPCRs μ receptor

______ does not dissociate in water: 1M X 1 particle per glucose molecule = 1 OsM glucose NaCl dissociates into two ions: Na+ and Cl 1M X 2 ions per NaCl = 2 OsM NaCl Molarity (mol/L) x Number of particles/molecule = Osmolarity (osmol/L)

Glucose

Excitiatory NT •______and possibly______ are the principal excitatory neurotransmitters in CNS • Major excitatory in bain • Releases glutamate • Uses_____ •The AMPA receptors are Na+ channels, NMDA receptor channel is permeable to ___- and ___ • Metabotropic are_________ and Ionotropic • In both cases_____ —EPSP

Glutamate aspartate astrocytes 7 transmembrane G proteins Ca2+ and Na+ DEPOLARIZATION

Pain modulation Slide 41 opioid—inhibit? • _____ and ______ are inhibited • Never reaches brain, no perception of pain Opioids • _____ , the source of morphine, is obtained from the poppy, Papaver somniferum and Papaver album. • Opium contains many alkaloids, the principle one being morphine, which is present in a concentration of about 10%. •______ remains the standard against which all drugs that have strong analgesic action are compared.

Glutamate and substance P Opium Morphine

Resting Membrane Potential Extracellular fluid 0 mV Intracellular fluid -70 mV •If a cell is permeable to several ions, we cannot use the Nernst equation, we use the____ ____ •Most cells ~ > 40 times more permeable to ___ than to ___ RMP Intracellular fluid extracellular fluid

Goldman equation K+ Na+ -70mV 0 mV

_____ • Sensory nerve fibers which are incapsulated within tendons • Arranged in series with muscle fibers, with one end attached to the ____ _____ fiber and the other end attached to the ____ fibers of the tendon • Provide information to CNS about the ____ or ____ applied to a muscle • Squeeze, and generate _______ and _____ OF MUSCLE

Golgi Tendon Organs: skeletal muscle collagen fibers load or force LOAD/FORCE AND LENGTH

OUT- DOWN Gradient; no energy IM UP GRADIENT; energy Diffusion •___ to _____ • Random movement of molecules from an area of ______ concentration of the molecules to an area of _____ concentration of molecules. • Perfume—move my diffusion, more concentration to less concentrated • When a crystal of dye (such as potassium permanganate) is placed in water, the crystal dissolves, and dye molecules spread by diffusion. • •Net movement of molecules occurs until concentration is equal everywhere = ______ . • The individual molecules are still moving at equilibrium, but for each molecule that exits the area another one enters =_____ _____

HIGH—>LOW higher lower equilibrium dynamic equilibrium

Increae K+ permeabiliy; ______ • Move out of the cell • INSIDE of the cell becomes even more ____ CLOSE The K+ channels • _____ , • Retains the K+ ions • Insides is ____ negative, depolarization •Na+, Ca2+ and Cl- have minimal permeability. Entry of Ca 2+ and Na+ => _____ , Cl entry=> _______ . • Most cells are fairly permeable to K+, but making them more permeable allows even more K+ to leak out => _______ . When the cell retains K+ it becomes more _____ and depolarizes.

HYPERpolization negative Depolarization less depolarization hyperpolarization hyperpolarization positive

Summation •_____ EPSP has a small effect on membrane potential - Produce a depolarization of about 0.5 mV - Could never result in an AP • Individual EPSPs can combine through_____ - Integrates the effects of all the graded potentials - Two types of summation • ____ _____ the same presynaptic neuron stimulates the postsynaptic neuron multiple times in a brief period o Overlapping in time •____ _____ multiple neurons all stimulate a postsynaptic neuron resulting in a combination of EPSPs which may yield an AP o If EPSP and IPSP—at the same time and cancel each other out and nothing happens

individual summation Temporal summation: Spatial summation :

Referred pain "Pain Gate" Theory •Ronald Melzack and Patrick Wall in 1965 proposed gate theory of pain, stating that the flow of nociceptive information through the spinal cord is modulated by simultaneous activation of the large myelinated fibers responsible for transmission of signals from low-threshold mechanoreceptors. • Example: rubbing your bumped head activates non-nociceptive touch receptors and diminishes sensation of pain. •According to the theory, the activity in the large nerve fibers that transmit sensation of touch would activate the ______ interneuron that would then block the neuron in the spinal cord responsible for transmission of information about pain stimulus.

inhibitory

Blistering Diseases: Pemphigoid and Pemphigus •Problems with a specific ____ (hemidesmosomes) and ______ (desmosomes) have been implicated in skin, oral mucosal and corneal lesions • Dysfunction of anchoring junctions the disease is called __________ o Blisters that do not heal

integrin cadherin Pemphigues

Receptor Physiology • The higher stimulus ______ is encoded as a higher ______ of APs in sensory neuron. • Information about the stimulus intensity is supplemented by ______ ______ , which refers to the number of receptors that respond to the same stimulus. • Increased action potential _____ encodes larger stimulus _____

intensity frequency population coding frequency intensity

Body cells are in contact with a privately maintained _____ environment • Each cell can make exchanges with its internal environment, but only particular body systems and specific cells can transfer materials between the ____ and _____ environment (e.g. digestive system, respiratory system). • Cells that exchange with external environment is the _____ _____ o *** listen

internal external and internal epithelial cells

The net result is entry of glucose into the cell against its concentration gradient, coupled to the movement of Na+ ____ the cell down its concentration gradient. The SGLT transporter can move glucose only into cells because glucose must follow ___ _____ Properties of carrier mediated transport (3)

into Na+ gradient. Specificity • Competition • Saturation

•The rate of diffusion is ______ proportional to the thickness of the membrane • The thicker the membrane, the longer the distance, the _____ the diffusion • For most biological membranes, the thickness is essentially constant. • Diffusion distance has pathophysiological role in _____ conditions in which the exchange epithelium of the lung is thickened with ____ ____ • If it gets thicker, it ___ down gas exchange

inversely slower lung scar tissue. slows

1. Sodium- potassium pump creates ___- ___ 2. Na+ glucose ______ transporter loading glucose from _____ 3. Na+-glucose symport transported releasing glucose into _________

ion gradient symport ECF cytoplasm

Cerebellar disease • Physical findings are _______ to the cerebellar lesion (i.e. the patient will fall toward the side of the cerebellar lesion) • _____ -inaccurate and poorly coordinated movements • _____ -inability to estimate distance as it relates to voluntary movement (finger-to-nose test)

ipsilateral Ataxia Dysmetria

Brown-Sequard syndrome •Because the mechanosensory (DCML) pathway ascends ______ in the cord, a unilateral spinal lesion will produce sensory loss of touch, pressure, vibration, and proprioception ____ the lesion on the same side •The pathways for pain and temperature cross the midline to ascend on the ____ side of the cord. Diminished sensation of pain below the lesion will be observed on the ____ ____ the lesion •Loss of pain and temperature sensation on one side of the body and of proprioception on the opposite side occurs with lesions that involve ___ half of the cord (Brown-Séquard syndrome). •The body surface is represented as a ____ _____ • Primary Somatosensory cortex or _____ _____ •Lesions in somatosensory cortex impair _____ sensations, and ____ -_____ evokes somatic sensations in specific parts of the ____ side of the body • It is discontinuous • (3) —larger representations in the somatosensory cortex

ipsilaterally below opposite side opposite one postcentral gyrus) somatic electrical stimulation contralateral Hand, mouth, tongue

************************************* 70 Epidermis: The skin surface is a mat of linked _____ fibers left behind when old epithelial cells die ____ _____ acts as the skin's main waterproofing agent ____ _____ produce keratin fibers ______ - anchor epithelial cells to each other • ______ are present in desmosomes • ______ are present in the hemidesmosomes Basal Lamina—anchoring junctions are hemidesmosomes Basal Lamina is the EM of the epithelial tissues ???

keratin Phospholipid Matrix Surface Keratinocytes Desmosomes CADHERINS INTEGRINS

SLIDE 33 The movement of material is driven by motor proteins: ____ powers anterograde transport, _____ powers retrograde transport. • Many infectious agents (herpesvirus, polio virus, rabies virus, and tetanus toxin) utilize ____ _____ to reach their site of action. • Oral herpesvirus enters nerve endings at the mouth and is transported to the ____ ___where it stays dormant for a period of time . •When reactivated, the virus replicates and returns to the ____ _____ causing a cold sore to form.

kinesin dynein axonal transport cell body axon terminal

Exocytosis releases molecules too _____ for transport proteins •Exocytosis takes place continuously in some cells, making it a constitutive process: • ___ ____ in the intestine constitutively release mucus by exocytosis. • In intestine epithelium • ____ —contain mucus and released into lumen by EXOCYTOSIS o Excreted by ____ ____ Secretion of mucus through ____ ___ o ____ role •In many _____ cells, hormones are stored in secretory vesicles in the cytoplasm and released in response to a _____ from outside the cell. • Stored _____ in vesicles in cytoplasm's • Then release them by ____ from signal

large Goblet cells Granules goblet cells, apical surface Protective endocrine signal hormones exocytosis

•In a muscle fiber, tension developed during a twitch is a direct reflection of the _____ of individual sarcomeres before contraction begins-each sarcomere contracts with optimum force if it is at the ___ ____ before contraction. •At the molecular level the sarcomere length reflects the _____ between thick and thin filaments.The sliding filament theory predicts that the tension a muscle fiber can generate is directly proportional to the number of _______ between the thick and thin filaments. _____ _____ ; muscle relaxes completely between stimuli • Single twitch does not represent a maximum tension that a muscle fiber can develop. The force generated by the contraction of the single muscle fiber can be increased by increasing the _______ at which APs stimulate the muscle fiber.

length optimum length overlap crossbridges Single twitches: frequency

The Molecular Basis of Contraction G-actin molecule • Tight binding in the rigor state • The Molecular Basis of Contraction 1. ATP binds to _____ , binding affinity for actin _____ . Myosin ______ actin. Myosin hydrolyses ___ . 2. Myosin head ____ and binds to a new actin that is __--___molecules away from where it started. a. ATP hydrolysis : ATP—ADP o Relaxed state with myosin heads _____ 3. Myosin Hydrolhyses ____ . Myosine head rotates and binds to _____ a. Newly formed actin-myosin crossbridge is weak and lowforce because ______ is partially blocking actin's binding site. Most resting muscle fibers are in this state prepared to contract, and just waiting for _____ signal 4. ____ ____ a. Actin filament moves toward ___ ___ b. The cross bridges transform into strong high-force bonds with release of ____ .Release of Pi allows the myosin head to _____ . The heads swing toward the _____ line, sliding the attached ____ filaments along with them. 5. Myosin releases ____

myosin decreases releases ATP rotates 1-3 cocked ATP actin tropomyosin Ca2+ Power Stroke M line Pi swivel M actin ADP

Rigor mortis-lack of ATP • Very brief 1. ATP binds to ____- a. Myosin _____- actin 2. Myosin hydrolyses -____ , myosin head rotates and binds to ____ a. _____ signal : relaxed state with myosin head cocked 3. ____ ____ 4. Myosin releases ___

myosin releases ATP actin Ca2+ Power stroke ADP

Myasthenia gravis reduces the efficiency of ______ ____ • Decline of amplitude of muscle _______ to repetitive stimulation of motor neuron • Prolonged and repeated activity Woreninng muscle weakenes with myasthenia gravis , Acetlycholinsterase nhibitior neostigamine, what is the performance in response to neostigmine treatment • Decrease ____ breakdown at NM junctions

neuromuscular transmission response Ach

NERVOUS SYSTEM DEGENERATIVE DISORDERS •Neurodegenerative disorders are characterized by progressive and irreversible loss of _____ from specific regions of the brain • •Examples of prototypical neurodegenerative disorders: o -____ _____ and ____ ___ where loss of neurons from structures of the basal ganglia results in abnormalities in the control of movement 2nd most common Mean onset is 57 years Can be early onset in some cases (juvenile parkinsonism, most likely genetically related)

neurons Parkinson disease and Huntington's disease,

Tonicity • Tonicity depends on the relative concentrations of ___________—cannot cross PM 1M and 1L of DIFFERENT solutions Hypotonic solution 1. Concentration gradient for water and solute a. Only water can more ______ concentration gradient i. HI to LO water ii. ______ to _____ Tonicity • Tonicity depends on _________solutes only Isotonic solution Hypotonic solution

nonpenetrating solutes (N) DOWN Hyper to hypo nonpenetrating

• Osmolarity depends strictly on the ____ of _____ per liter of solution and says nothing about what the particles are or how they behave. • To predict whether osmosis will occur, we need to know the properties of the _____ and ____ on each side of it. Picture 51 * • If the membrane is permeable only to water and not to any solutes, water would move from ____ concentrated (_______ ) solution to ____ concentrated (______ solution). •Biological membranes are semipermeable, and they allow some solutes to cross in addition to water. To predict the movement of water into and out of the cells we need to know the _____ of the solution. • The tonicity of the solution is always described relative to the cell: it describes the cell _______ once the cell has come to equilibrium with the solution. o Only relative term that describes the cell

number particles membrane solutes less hyposmotic more hyperosmotic tonicity volume

• Organs (7)

o Eye o Ear o Brain o Heart o Skin o Uterus o Intestines

Organization of movement control Slide 35*** Descending Systems • Upper Motor Neurons ____ ____ Planning, initiating, and directing voluntary movements ____ _____ • Gating proper initiation of movement ______ : Sensory motor coordination o Brainstem centers Basic ______ and _____ control • Local Circuit neurons: _____ ______ • Motor Neuron Pools: ____ ____ neurons Skeletal muscles

o Motor Cortex Basal Ganglia Cerebellum movements and postural reflex coordination

Each type of receptor is specialized to respond more readily to one type of stimulus, its _____ stimulus (stimulus for which it has _____ threshold of detection): • ______________________ o gustation - taste; o olfaction - smell; o O2, CO2, o pH, o osmolarity • ________________ o stretch, tissue displacement, vibration • _________ o pain • _____________ o hot, cold • ___________ o light

one adequate lowest Chemoreceptors Mechanoreceptors Nociceptors Thermoreceptors Photoreceptors

Concentration gradient Electrical gradient Artificial cell with inserted K+ leak channel • the only force was concentration gradient, K+ would leak out until concentration would be the same inside and outside. • Because opposite charges attract, the Pr- inside the cell will try to pull K+ back into the cell • . At some point the electrical force attracting K + inside becomes equal in magnitude to concentration gradient driving K + out => net movement of K + across the membrane stops. ** In a cell that is permeable only to one ion, the membrane potential that exactly _____ the concentration gradient of the ion is known as the ___ ____of that ion, or Eion . ___ gradient and ____ are equal- the system is in equilibrium

opposes equilibrium potential Electrical concentration

• Overlap prevents crossbridge formation • The filaments begin contracting with numerous cross bridges, allowing the fiber to generate ______ force • In the initial part of contraction, the sliding filaments interact only _____ and can't generate much force

optimum minimally

Internal structure of a Skeletal Muscle Orderly arrangement of muscle cells and connective tissue • Whole muscle (an _____ ): ______ (bundles of muscle cells) • Muscle _____ (individual cells) o Nuclei on skeletal muscle are pushed to the ______ because of the number muscle fibers • ______ (intracellular structure) • _______ (myosin and actin) Each cell or muscle fibers- _____ Group of cells- Fascicle--- covered by a _______ Covers entire muscle(many fascicles)—_____

organ Fascicles fibers periphery Myofibrils Myofilaments endomysium perimysium epimysium

Anatomical differences: • Anatomical difference: o Pathway point of _____ in CNS o Location of _____- ganglia • Sympathetic pathways originate in the _____ and _____ regions of the spinal cord o Sympathetic ganglia are found primarily in ____ chains that ran along either side of vertebral column o Short ______ neurons and long _____ fibers • Many parasympathetic pathways originate in the ____ ______ , and their axons leave the brain in several ______ nerves o Some parasympathetic pathways originate in the _____ region of the spinal cord and control ____- organs o preganglionic and short postganglionic fibers o Parasympathetic ganglia are located either ___ or ____ their target organs o Most internal organs are under ______ control: one autonomic branch is excitatory and the other branch is inhibitory

origin autonmonic thoracic and lumbar two preganglionic postganglionic brain stem cranial sacral pelvic on or near antagonistic

Optimal resting length—little overlap • Shorten in beginning of contraction more ____ —more active crossbridges--- more tension and force can be generate by skeletal muscle • Optimal—overlapped actin and myosin o If it is shorter than optimal length, less to movement, and prevent normal formation of cross bridge and ____ or _____ decreases • If overlapped too much, tension decreases rapidly

overlap tension or contraction

Neuropathic pain •Lesions of the peripheral or central nociceptive pathways typically result in a loss or impairment of ___ ____ •Paradoxically, damage to or dysfunction of nociceptive pathways due to ____ ______ can also produce pain (e.g. diabetes, herpes zoster) • Neuropathic pain may also be produced by damage to the CNS, following _____ or _______ injury to spinal cord, brainstem, or thalamic areas that contain central nociceptive pathways •Neuropathic pains are often severe and are typically resistant to standard treatments for pain •____ are not effective; _____ are partially effective and their long-term use poses the risk of dependence; _________ (SNRIs, TCAs) and antiepileptic drugs are useful in some patients for neuropathic pain. • Tingling, different than the rest of pain

pain sensation neuron degeneration trauma or cerebrovascular NSAIDs opioids antidepressants

Osmolarity describes the number of _____ in solution Mole is 6.02 X 10 23 molecules (Avogadro's number) Molarity = ___________ -one glucose molecule in H2O yields 1 particle, but one NaCl dissolved in H2O yields 2 particles: Na+ and Cl-. Water moves by osmosis by ______ ** -H2O moves by osmosis in response to total _____ of _____ in the solution => biological concentration of molecules is expressed as __________ , the number of particles (ions or intact molecules) per liter of solution: ______________= Osmolality (osmol/L)

particles Moles of solute/ liters of solution Mol/L PARTICLES concentration particles osmolarity Molarity (mol/L) x Number of particles/molecule

The Senses Our _____ is our reality •Perception is our____ _____ of the external word as created by the brain from a pattern of ______ ______ delivered to it from sensory receptors.

perception conscious interpretation nerve impulses

Receptor Physiology • Specialized ending of afferent neuron • Specialized cell closely associated with the _______ ending of _____S neuron • Stimulation of the receptor alters its ____ ______ , leading to a graded receptor potential. • The stronger the stimulus, the greater the permeability change and the larger the ____ ____

peripheral afferent membrane permeability receptor potential.

Excitatory and Inhibitory Postsynaptic Potentials (EPSPs and IPSPs) • Some NTs increase______ of Na+ channels, which results in a ___ ____ • Graded depolarization will bring the neuronal VM closer to threshold. Thus, it's often referred to as an _____ • Some NTs increase permeability for K+ or Cl-, which results in a ____ ____ • Graded hyperpolarization will bring the neuronal VM farther away from the threshold. Thus, it's often referred to as an ____ • In we increase ___ concentration—depolarization of the post synaptic—_____ probably of AP - EPSP • Others increase permeability to __ or ____ ions, Hyperpolarization, moves further away from threshold- IPSP

permeability graded depolarization excitatory postsynaptic potential or EPSP graded hyperpolarization inhibitory postsynaptic potential or IPSP Na+ increase K+ or Cl-

Phospholipid Bilayer • Determines passive _____ of membranes (diffusion) _____ soluble molecules permeate or diffuse through phospholipid bilayer easily -____ soluble (hydrophilic) do not * cannot pass through membrane by ___ ____ * ONE exception is ______ , since it is so small, it can cross by simple diffusion • Aquaporin's

permeability -lipid soluble (lipophilic) water simple diffusion WATER

•The rate of diffusion depends on how ______ is the membrane to the diffusing molecules. Only _____, _____ and _____ molecules can move across membrane by simple diffusion. • _____ may diffuse across phospholipid membranes. Membranes with ____ cholesterol content are less permeable to water.

permeable lipids, steroids, and small lipophilic Water high

Etiology and Pathogenesis of PD • Most PD cases occur sporadically (85-90% ) and are of unknown cause • Epidemiologic studies suggest increased risk with exposure to _____ , ______ living, and drinking well water and reduced risk with ___ ___ and _____ • About 10-15% of cases are familial in origin, and multiple specific mutations and gene associations have been identified (e.g. parkin, alpha-synuclein) • It has been proposed that most cases of PD are due to a "double hit" involving an interaction between a gene ______ that induces susceptibility coupled with exposure to a ____ environmental factor.

pesticides rural cigarette smoking and caffeine. mutations toxic

Composition of Cell Membranes Lipids: (3) Proteins: (3)

phospholipids, glycolipids, cholesterol integral, peripheral, lipid-anchored

•Positive Babinski's reflex (upturned toes when the lateral edge of the sole is stroked with the blunt object; the normal response is downturned toes and is referred to as ____ ___ • Positive (bad) toe extension • Good/normal-_____ of toes o Up to two years old—toe extension In somatic motor pathways, the axons of ____ neurons extend out of the CNS to innervate skeletal muscles • ____ ____ ____ those neurons have their axons terminate directly on muscle 9 year old tina falls while climbing tree on her back. Her frightened parents take ER to the local ER where she is examined. He knee jerk(______ ) is normal and she exhibits a neg. Babinski reflex (_____ ) These observations suggest that • No damage to ____ ___

planar response) flexion lower motor neurons Lower Motor Neurons— lower upper spinal cord

•The ____ ______ and supplementary motor area are involved in the selection of appropriate motor plans for voluntary movements, whereas the _____ ____ ______ s involved in the execution of these voluntary movements. •Stimulation of premotor cortex or the ____ ____ _____ requires higher levels of current to elicit movements, and often results in more_____ movements than stimulation of primary motor cortex. •When either premotor cortex or supplementary motor area is damaged, the person can not process ____ _____ information to accomplish purposeful movement in a spatial context.

premotor cortex primary motor cortex supplementary motor area complex complex sensory

Botulinum toxin • Botulism is a neurologic syndrome caused by a toxic proteolytic enzyme produced by the bacterium Clostridium botulinum - spore-forming, obligate an aero be found most commonly in soil. • Botulism can result from ingestion of contaminated food, colonization of the gastrointestinal tract in an infant, or wound infection. Many of the deaths associated with botulism resulted from exposure to improperly _____- and _____ foods. • Used for muscle _____

prepared canned excitability excitability

Sodium-potassium pump - ____active transport •Maintains the concentration gradients of Na+ and K+ across the cell membrane. •Pumps ___ Na+ outside the cell and ____ K+ into the cell for each ____ consumed. Primary Active Transporters called ATPase or protein pumps • Sodium Potassium Pumps • ATpase • ATPases or proton group

primary 3 2 ATP

Blood-brain barrier (BBB) •BBB _____ the delicate brain and spinal cord • Blood borne pathogens NEGATIVE SIDE: Limits the use of drugs for the treatment of CNS disorders because many drugs are unable to penetrate BBB • Challenge to drug design, functionally active and able to cross BBB

protects

Electrical Synapses • Gap junctions contain ____ ____ that allow ions to flow between adjacent cells • Found in ____ and _____ muscle and some neurons & glia • Allows the action potential of the presynaptic cell to be propagated to the postsynaptic cell • _________ (two-way), very fast • Site of cell communication—___ _____ channels that connect the interiors of neighboring cells • Two consqeuences o ______ —just depends which neurons fires an AP first o Because flow thru gap junctions is continues, very rapid • More general function, synronize the ????

protein channels (connexons) cardiac & smooth Bidirectional gap junctions- Bidirectional

Cytoskeleton—all _____ _______ ; movement and migration, all essential for _____ • ______ (microfilaments) o Smallest of protein fibers • _____ ______ ______ in epithelial cells, _______ in nerve cells ______ in muscle, _____ in mesenchymal cells) • Microtubules made of ________ • Microvilli

protein fibers movement Actin Intermediate Filaments keratins neurofilaments desmin vimentin tubulin

Extracellular matrix (EM) consists of different combinations of _____ _____ (collagen, reticular, and elastic fibers) and _____ ______ •Ground substance is a highly _____ , viscous complex of _____ ________ (glycosaminoglycans and proteogycans) and _____ (laminin, fibronectin, etc.) Lumen of Gut Basal Lamenla—EM in epithelial cells • Cells are held together by ______

protein fibers ( ground substance hydrophilic anionic macromolecules glycoproteins junctions

Corticospinal tracts Anterior Corticospinal Tract: to____ muscles Lateral Corticospinal tract: to______ muscles • ~ 90% of axons that project from the primary motor cortex to the spinal cord are contained in the ____ _____ tract. The 10% of cells have axons that do not cross at the medulla, and travel in the ____ _____ tract in the spinal cord. • Major pathway in which brain communicate to spinal cored o To initiate and control voluntary movement

proximal limb lateral corticospinal anterior corticospinal

Cytoskeleton •Serves as intracellular "____ ___" for moving organelles •Special ______ ______ (myosins, kinesins and dyneins) facilitate intracellular transport by using energy from ____ to slide or step along the cytoskeletal fibers •Most motor proteins have two heads which alternatively bind to the _____ ______, a -___ , and a ____ region that is able to bind "cargo"

railroad track motor proteins ATP cytoskeletal fiber neck tail

Direct pathway (e.g. reflex) • Senses and action (___) Indirect pathway • Cognition—_____- • Cognition-____ Key concepts in motor control: Functional Segregation: • • The motor system is divided into a number of different areas that control different aspects of movement (a "___ and ____ " strategy). • Motor system is_____ into different areas

reflex action senses divide and conquer divided

DMD has a prevalence of ~ 1:3500 live male births. It affects young boys, who first show loss of strength in their proximal muscles, leading to a waddling gait, difficulty in standing up, and eventually very severe weakness. Death generally occurs from ______ insufficiency.

respiratory

Antidepressant therapy • Many drugs used to treat depression either block NT______ (tricyclic antidepressant drugs ( TCAs), SNRIs, SSRIs) or inhibit NT enzymatic ____ ______ (MAO inhibitors) • MAO inhibitor—inactivatives noeph and sertone, increase of secretion of ???????? o Inhibit Noeph, serotine and start to accumulate in synaptic cleft, enhances activation of post synaptic receptors • The overall result is increased ____ _____ in the synaptic cleft. • _____the most widely prescribed drug in American psychiatry, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. o Only serotonin NT, and reuptake to the pre-synaptic terminal

reuptake break down NT level Prozac (fluoxetine),

Sliding Filament Model During muscle contraction, each _____ shortens as the thin filaments slide inward between the thick filaments so that _____ lines are pulled closer together. _____ signals initiate contraction Relaxed state. Myosin head ______ . 1. _____ levels increase cytosol a. Increase _____ Ca_ 2. Ca2+ binds to ______ 3. Troponin-Ca2+ complex pulls ______ away from the actin's myosin-binding site a. Tropomyosin shiirfts, exposing ___- _____ on actin 4. _____ binds to actin and complete ____ ____ a. _______ moves 5. Actin Filament moves

sarcomere Z lines Calcium cocked Ca2+ cytosolic TN (troponin) tropomyosin binding site Myosin power stroke Actin

Tight Junction Structure • Branching network of ____ ______of tight-junction proteins • surrounding whole cell - "______ " o Sometimes called the quilted junctions They prevent _____ between cells _____ : anchor cells to each other Cell Junctions Chart *** 76 Function: Communication Location:___ - _____ junctions Type: _____ junctions Membrane protein: ______

sealing strands quilted movement Desmosomes cell-to cell Gap Conexin

Sensory Neurons: Two-Point Discrimination • Compass with points separated by 20 mm • Skin surface • Primary sensory neurons • Secondary sensory neurons • One signal goes to the brain • Slide 13- two signals go the brain •The size of ____ _____ ____ determines how sensitive a given area is to stimulus •Two-point discrimination varies with the _____ of the secondary receptive field • More sensory—receptor fields are _____ —we stimulate two different receptor fields • Depends on the ____ RECEPTOR FIELDS

secondary receptive field size smaller SMALLER

Afferent- _____ input Efferent- ______ output Divisions of the Nervous System • Autonomic nervous system can be further divided into: • -Sympathetic Nervous System o •"____ or ____ " • -Parasympathetic Nervous System o •"____ and ____ " o Digestion • Most of the time there is a ____ between the autonomic braches

sensory Motor Fight or Flight Rest and Digest balance

• Afferent, Efferent, and Interneurons • Afferent—activated by ____ input o The AP is generated long the ____ _____ to the CNS o Only a small amount • Effect - cell body is within the CNS—leaves to go to organs • _______ —entirely within the CNS (99% of our neurons_ o Dual function Integration ______ response Interconnection btw ______ themselves, ________________________ • Least understood

sensory axon terminal Interneurons peripheral interneurons complex activing, thinking (mind)

Cytoskeleton plays an important role in determining the _____ of the cell • _____ increase cell surface area o They are supported by ______ o Increase _____ _____ ______ : Form a network just inside the cell membrane • ______ : Are the largest cytoskeleton fiber • Intermediate filaments o Include ____ and _____

shape Microvilli microfilaments fast absorption Microfilaments Microtubules myosin and keratin

Diffusion occurs rapidly over ____ distances and slowly over ____ distances •Importance of ____ membrane for gas exchange across alveoli •Gas exchange in the lungs is rapid, blood flow through pulmonary capillaries is slow, and diffusion reaches equilibrium is less than 1 sec. • Make diffusion as fast as possible for gas exchange

short large thin

Motor neurons •Neurons in the ventral horn, which innervate ____ ____ and cause the muscle contraction are called ____ ____ ____ •Motor neurons are clustered in columnar, spinal nuclei called _____ ____ _____ . All of the motor neurons in a motor neuron pool innervate a_____ muscle, and all motor neurons that innervate a particular muscle are contained in the same ___ ___ ___

skeletal muscle alpha motor neurons motor neuron pools single motor neuron pool.

Endocytosis is an active process, requires ATP • Vesicles created by endocytosis are ____ than in phagocytosis • Can be _____ , allowing some fluid to pass inside the cell-______ • ______ ______endocytosis is highly selective, allows only specific molecules to enter the cell ______ —fuses, the exported into ECF

smaller nonselective pinocytosis Receptor-mediated Exocytosis

Neurons (nerve cells) • Cell body-_________ • Cell processes that extend from the soma and receive input-_______ • Cell processes that extend from the soma and primarily transmit action potentials (output)-________ • Axon originates from a special region of the cell body called the _____ ____ • The myelin sheath is made by ________ in the CNS and by _________ in the PNS CNS— myelin by the ________ PNS- _______ • Interspersed along the axon are gaps where there is no myelin -_______ • Highly abundant rough ER (site of protein synthesis) =___ ____

soma (perikaryon) dendrites axons axon hillock Oligodendrocytes Shawnee cells nodes of Ranvier Nissl bodies

KEY POINTS • Sensory information that reaches the level of conscious awareness includes (1) ______ sensation and (2) _____ ____ • Perception is the _____ interpretation of the external world that the brain creates from _____ input • Each type of sensory receptor responds to its _____ ______ a change in the energy form or modality to which the receptor is responsive) • A stimulus brings about a _____ ___ ______ l, which in turn is able to generate APs • The _____ of stimulus determines the amplitude of the receptor potential, which in turn determines the _______ of APs • Receptor potential size is also influenced by _____ -____ • The term _____ _____ refers to the area surrounding a receptor within which a receptor is able to detect stimuli • All somatosensory information from limbs and trunk is conveyed by ____ ____ -_____ neurons •______________________ sensory pathway conveys fine touch and vibratory input and ____ _____ tract conveys pain and temperature sensory input • The body surface in the primary sensory cortex is represented as a _______

somatic special senses conscious sensory adequate stimulus ( graded receptor potential intensity frequency receptor adaptation receptive field dorsal root ganglion Dorsal column-medial lemniscus (DCML) spinothalamic (anterolateral) somatotopic map ("homunculus")

1. Pain can be modulated by simultaneous -_____ input 2. Touch or nonpainful stimulus and painful stimulus 3. Painful stimulus _____ a. Send ______ information, reduced perception of pain The brain has a built-in analgesic system ___________ system pathways selectively target the nociceptive relay neurons in the spinal cord inhibiting the transmission of painful stimuli. • Periaqueductal gray matter (PAG) and rostal ventral medulla (RVM) •Two main regions are known to be the part of the descending analgesic pathway: _____ and _____

somatosensory decreased inhibitory •Built-in analgesic periaqueductal gray matter (PAG) and rostral ventral medulla (RVM)

Axoplasmic transport The length of the axon affects ____ . Synthesized in ___ ____(CNS), and released at ____ _____ Axoplasmic transport—microtubules function are tracts from body to axon terminal • Cell body -to axon terminal • Axon terminal cell body called ______ ____

speed cell body axon terminal Anterograde transport retrograde transport

**************************** 3 (3) Regulate different processes • NS—________ • Endocrine—_____ The functional function of both systems are connected • ?? called • Act as a single ___ ___ Nervous system: • _____ anatomical connections with the target cells ("wired" system) •____ _____ (neurotransmitters) usually diffuse a very short distance (synaptic cleft) • acts rapidly for a ____ period of time (msec, sec, min)

speed duration functional unit close chemical messengers short

Phospholipids in water •In water amphipathic molecules aggregate in _____ clusters. •Their polar regions form _____ _____ with water molecules at the surface of the cluster, while the ___ ____ regions cluster together away from water. Head- form hydrogen **** slide 31 Amphipathic Lipid Head •_____ or ______ groups • "water loving" Tail • -____ or ______ groups • "water fearing"

spherical hydrogen bonds non-polar Polar or hydrophilic Nonpolar or hydrophobic

Somatic Senses Pathways 1. Pain, temperature, and coarse touch cross the midline in the ___ ___ 2. Fine touch, vibration, and proprioception pathways cross the midline in the ______ 3. Sensory pathways synapse in the ______ 4. Sensations are perceived in the ____ _____ _____ cortex ______ sensory neurons from Spinal Cord to thalamus _____ sensory neurons from Medulla to Spinal Cord

spinal cord medulla thalamus primary somatic sensory Secondary Primary

Spinal cord •Major conduit of sensory and motor information between the brain and periphery; connected to the periphery via ___ _____ which are part of PNS •Each spinal nerve attaches to the spinal cord by two branches, a_____ root and a___ root. • The dorsal root brings_____ information • the______ root carries away efferent information

spinal nerves, dorsal ventral afferent ventral

Stretch Reflex- Knee jerk reflex ** slide 15 1. Extensor muscle____ 2. ___ _____ stimulated 3. Primary______ neuron excited 4. Primary AFFERENT neuron stimulates _____ ____ ____ to extensor muscle 5. AMN stimulates extensor muscle to_____ 6. Primary AFFERENT neuron stimulate _____ _____ 7. Interneuron inhibits AMN to_____ muscle 8. Flexor muscle (antagonist)_____

stretch Muscle spindle AFFERENT alpha motor neuron contract inhibitory interneuron flexor relaxes

Basal ganglia form set of interconnected nuclei in the forebrain: •______ (caudate nucleus and putamen) • ___ _____ •_______ nucleus • ____ _____ of the midbrain (although not part of the forebrain, it's functional part of the basal ganglia)—midbrain o Functional part of basal ganglia Connections between cortex and basal ganglia- ____ ___ Direct pathway-_______ net effect Indirect pathway-_____ net effect Dopaminergive neurons from ____ ______ stimulate the direct pathway and inhibit the indirect pathway

striatum globus pallidus subthalamic Substantia nigra motor loop excitatory inhibitory SUBSTANTIA NIGRA

Functions of Integral Proteins •_____ ______ connection of cell membrane to another cell, extracellular matrix or cytoskeleton inside the cell packaging of different ___ and _____ Functions of Integral Proteins •____ ____ ____ (especially glycoproteins) o _______ ;; sugar (CHO) chain attached o Used a cell identity marker o CD20—only ____ _____ cells - indenity Very important in diagnostics

structural proteins - cells and tissues cell identity markers Glycoproteins mature B

Channel proteins • Channel proteins are named according to the _____ they allow to pass. • Most cells have water channels made from protein called _____ . • In addition more than 100 types of ion channels have been identified: Na+, K+, Ca2+, Cl- channels. • The selectivity of the channel is determined mainly by the ______ of the pore and ____ ____ of aminoacids that line the pore • Depends on o Size of ____ o Charge on ___ Negative will affect positive and allow them to pass

substance aquaporin diameter electrical charge pore AA

Neuropathology of PD The ___ ____ in a normal individual appears as a black line on postmortem examination due to the presence of large pigmented neurons that produce DA. The substantia nigra becomes _____ (loss of pigmented neurons) in PD with the loss of neurons. • Pathologically, PD is characterized by severe loss of substantia nigra (SN) dopaminergic neurons. • It is estimated that ~ 60% -70% of the SN dopamine cells are lost by the time a patient first presents for clinical evaluation, diagnosis, and treatment. • Loss of dopamine terminals in the striatum progresses over time.

substantia nigra pale

Carrier mediated transport saturation ?? • The rate of substrate transport depends on the _____ ______ and the ______ of carrier molecules. • For a fixed number of carriers as substrate concentration ______ , the transport rate _______ to a maximum, a point at which all carrier binding sites are occupied with substrate. At this point further increase in substrate concentration has no effect. • They have the ability to _____ saturation Which form of transmembrane transport does NOT require a membrane protein? ____________

substrate concentration number increases increases regulate • Simple Diffusion

Principle Functions of Cell Membranes—essential for _____ of cell, _____ of the cell, and ____ ___ • Structural ____ of Organelles • _____ of materials with eternal environment • Exchange of _____ (signals) with external environment (reactions) _____ of the cell with surroundings ____ -____ —transmit information into cell, changes response to changes in cell ??? Binding—changes the _____

survival boundary Physical Isolation (Barrier) Support Exchanges information Interaction Membrane receptors intracellular

Drugs that act on ___ _____ in CNS are the oldest known and most widely used of all pharmaceutical agents (1) AP in presynaptic fiber (2) Synthesis of ________ (3) Storage of NT (4) Metabolism of NT (5) ______ of NT (6) Reuptake of NT into the ____ ____ or uptake into a ____ ____ (7) _____ of NT (8) Receptor for the NT ( 9) Receptor-induced increase or decrease in ionic ____ (10) ____ signaling

synaptic activity neurotransmitter (NT) Release nerve ending glial cell Degradation conductance Retrograde

Glia-more than just brain glue? • Dynamic and equal parts for synaptic transmission • Pre-synatic terminal - and astrocytes same NT o Releases substances—glia transmitters o Glia cells can actively participate in ____- _____

synaptic transmission

Antrphieptic drug vigabatrin acts by irreverabilty inhibiting the enzyme GABA transaminase, which breaks down GABA into inactive metabolites, Vigabatrin administration results in • Enhanced GABA-mediated ____ ____ Which of the following is not a known drug effect on synaptic function? • Change the____ of NT found in the synaptic vesicle

synaptic transmission type

Diffusion is directly related to temperature •At higher temperature molecules move faster => the rate of diffusion increases as temperature increases. = rate of diffusion increases •Changes in ______ do not significantly affect diffusion rate in humans because we maintain a relatively constant body temperature. Diffusion rate is ______ related to molecular size •The larger the molecule, the slower its diffusion through given medium.

temperature inversely

History of Parkinson Disease • Parkinson's disease (PD) was first described in 1817 by James Parkinson, a British doctor who published a paper on what he called "___ __ _____ " In this paper, he described the major symptoms of the disease that would later bear his name. • Public awareness campaigns include Parkinsons disease day on the birthday of James Parkinson, April 11.

the shaking palsy.

KEY POINTS •Sympathetic pathways originate in the ____ and _____ regions of the spinal cord. Most sympathetic ganglia are located close to the ____ ____ (are paravertebral). Parasympathetic pathways leave the CNS at the brain stem and in the -____ region of the spinal cord. Parasympathetic ganglia are located close to or in the ___ -____ •Both parasympathetic and sympathetic pathways consist of ___ _-___ (preganglionic and postganglionic) in series. One exeption to this rule is the ____ ____ , in which postganglionic sympathetic neurons have been modified into a ____ organ. •_____ is released at nerve terminals of all preganglionic neurons, postganglionic parasympathetic neurons, and a few postganglionic sympathetic neurons (sweat glands). The remaining sympathetic postganglionic neurons release ___ . •Many common drugs exert their therapeutic actions by serving as ____ or ____ at autonomic synapses. •______ activity prepares the individual to cope with an emergency _______ activity is concerned with the vegetative aspects of day-to-day living.

thoracic and lumbar spinal cord sacral target tissue. two neurons adrenal medulla neuroendocrine ACh NE agonists or antagonists Sympathetic Parasympathetic

A receptor can only transduce a stimulus that is applied to a restricted area, or a receptive field of this receptor. Slide 11 • The receptive fields of _____ primary sensory neurons overlap to form one large secondary ____ ______ • Information from the ______ receptive field goes to the brain. • The primary sensory neurons converge on one secondary sensory neuron. • Smaller receptor field, ?????

three receptive field. secondary

Blood-brain barrier (BBB) • In the brain capillaries the cells are joined by ____ ______ : lipid soluble substances, O2, CO2, alcohol and steroid homones penetrate endothelial cells by dissolving in their plasma membrane •_____ , ___ _and ___ are transported by highly selective membrane-bound carriers • No carried or molecules to move across the epithelial cells, can't cross BBB •Transport between the capillary cells is anatomically prevented and transport through the cells is physiologically restricted=____ •_______ signal the cells forming the brain capillaries to "get tight" • Needs to cross two membranes o ______ membrane o _____ membrane _______, ______, ______molecules can easily cross the PM and BBB

tight junctions Glucose, amino acids and ions BBB Astrocytes Plasma Blood Water, gases, and lipophilic

All muscle fibers in a single motor unit are of the same fiber________ : fast-twitch motor units and slow-twitch motor units. •Muscle can vary contraction force and duration by • 1) changing the ______ of motor units that are active • 2) changing the ______ of motor units that are responding at any one time.

type types number

Summation of Contractions: ____ _____ • If APs continue to stimulate the muscle fiber at high frequency, relaxation between contractions diminishes until the muscle fiber achieves a state of maximal contraction-tetanus. Summation of Contractions: ____ _____ • •Although motor neuron innervates multiple muscle fibers, each muscle fiber is innervated by only one motor neuron. • No time to relax at all, tension increases until tetanus - complete—no relaxation at all • Fatigue causes muscle to lose tension despite ____ stimuli

unfused tetanus complete tetanus continuing

Continuous conduction • Occurs in ______ axons •An AP in a _____ _____of a membrane stimulates the opening of voltage-gated channels in the adjacent area of membrane so that the AP is propagated over the entire surface of the cell Saltatory conduction •Occurs in ____ axons •When AP occurs at one ____ , opposite charges attract from the adjacent inactive node, bringing potential to threshold so that it undergoes an AP, and so on •Saltare is a Latin word meaning "to leap"

unmyelinated local area myelinated node

Sympathetic Neuron 1. AP arrives at _____ 2. Depolarization opens voltage-gated _____ channels 3. Ca2+ entry triggers_____ of synaptic vesicles 4. NE binds to ______ receptor on target 5. Receptor activation _____ when NE diffuses away from the synapse 6. ____ is removed from the synapse 7. NE can be taken back into synaptic _____ for re-lease 8. NE is metabolized by ______

varicosity Ca2+ exocytosis adrenergic ceases NE vesicles monoamine oxidase (MAO)

The basal ganglia receive a large amount of input from cerebral cortex, and after processing, send it back to cerebral cortex via ____ _____ ______ of thalamus=motor loop • Direct pathway from the putamen suppresses the inhibitory output from the internal segment of the ___ ____ on VLN of thalamus=_____ net effect • Indirect pathway is conveyed through the ____ ____ . Exitatory neurons from subthalamic nucleus boost the activity of inhibitory output neurons and suppress VLN=______ net effect • Dopaminergic neurons from ____ _____ regulate motor behavior by stimulating the direct pathway and inhibiting the indirect pathway

ventral lateral nucleus (VLN) globus pallidus excitatory subthalamic nucleus inhibitory substantia nigra

Membrane Transporters: directly incorporated into lipid bilayer •create _____ -filled passageways that directly link the ______ and _____ compartments •bind to the substrate they carry but never form a _____-- connection between intracellular and extracellular fluid. ____ ______ allow rapid transport across the membrane but are limited to moving ___ ____ and _____ ______- , while slower, can move larger molecules. • Ion channel - move smaller molcules o Continuous • Carriers—bigger o Only one side of cell o Not ______

water intracellular and extracellular direct •Channel proteins small ions and water. Carriers continuous

Osmosis and Osmotic Pressure 1. Two compartments are separated by a membrane that is ONLY permeable to _____ but not glucose. a. Selectively permeable membrane 2. Water moves by osmosis into the ____ concentrated solution a. Volume decreased = volume increase 3. ___- _____ is the pressure that must be applied to B to oppose osmosis. a. Volume equals •The pressure that must be applied to exactly _____ the movement of water is known as the osmotic pressure of solution B. The units of osmotic pressure are ___________ ), or________

water more (more solute) Osmotic pressure oppose atmospheres (atm millimeters of mercury (mm Hg).

Typically patients present with extraocular muscle weakness at first, which can lead to ptosis (drooping eyelid) and diplopia (double vision), and later develop limb and bulbar muscle weakness. • Worsening of _______ after prolonged and sustained muscle contraction (fatigability) is the hallmark of MG.

weakness

Control of Homeostasis NS • "____ " system o _____ usually diffuse a very short distance o Acts ____ for a short period of time Endocrine • "_____ " system • Hormones carried by the ____ • Acts _____ for a ____ period of time

wired Neurotransmitters rapidly wireless blood longer

Neuropathology of PD • Neurons in CNS of PD patients have abnormal accumulation of the protein called____ ___ • Particularly numbers in SN • This insoluble protein accumulates inside neurones forming inclusions called __ ____ (first described by in 1912 by a German neuropathologist Friedrich Lewy) •____ ______gene has been linked to autosomal dominant PD, but the exact molecular mechanism remains unknown Lewy Bodies - Immunohistochemistry

α-synuclein Lewy bodies α-synuclein

_____ _____ • Produce ATP by themselves, then use the ATP Sodium-potassium pump o Hydrolysis ATP, then uses that ATP to move sodium across membrane o Na+-K+-ATP-ase uses energy of ATP directly to push Na+ and K+ ______ their concentration gradient. •Secondary active transport uses energy _____ in the concentration gradient of one molecule, to ____ other molecules ______ their concentration gradient. ________ uses Na+ concentration gradient to push glucose inside the cell against its concentration gradient o _____ use energy of one molecule

• ATP hydroloysis against stored push against SGLT SDGT - Sodium dependent glucose transporter

The protein that makes up the thinnest intracellular filaments is _____ In contrast, intermediate filaments of sarcomas, tumors that arise from transformed cells of mesenchymal origin show different markers ___________ • positive staining of the malignant cells for keratin 7, which confirms the _____ origin of the tumor • ______ _______ are intracellular compartments separated from cytosol by phospholipid membranes • ______ dangerous substances • The _______ created by organelles allow the cells to isolate substances that might be harmful to the cell (digestive enzymes) and separate functions •(5)

• Actin—microfilaments (vimentin, desmin) epithelial Membranous organelles Isolate compartments Mitochondria, endoplasmic reticulum, Golgi complex, lysosomes and peroxisomes

The junctions that allow direct communication between cytoplasm of adjacent cells as __________ The disappearance of _____ junctions occurs when cancerous cells metastasize • The space that is surrounded by the tissue wall of hollow organs is known as ______

• Gap junctions Anchoring LUMEN

Resting cell membranes are most permeable to _________ At equilibrium when the cell is at rest, • The concentration of ______ ions is higher inside the cell What happens to the membrane potential of a cell that suddenly becomes more permeable to NA+ • __________ The most concentrated anion in ECF • ______

• K+ K+ Becomes more positive—depolarizes Chloride LOOK AT SLIDE PICTURE

An increase in which of the following will decrease the rate of diffusion of a molecule across a cell membrane? _____________ • _____________ - increase • The steeper the _________, the bigger the difference, the molecules will move fast across membrane to make it equal

• Molecular size concentration gradient concentration

Muscle Contraction creates force ____ _____ : force created by contracting muscle • _____ : weight that opposes contraction • _______ : creation of tension in muscle, active process requires energy input from ATP. • ______ : release of tension

• Muscle tension Load Contraction Relaxation

Action potential ____ channels open • Na+ ions enter the cell • _______ Stages • Depolarize—Na+ open • Action potential ____ leaves—repolarization

• Na+ Depolarization • K+

The spinothalamic tract crosses the midline at which level of the nervous system? ___________ The dorsal columa— ____ During a brain surgery, part of DCML system was exposed and stimulated • ____________________

• Spinal Cord Medulla Feeling as if something were touching his index finger

How does the loss of the dopaminergic neurons cause the poverty of movements associated with Parkinson's disease? ______________________ • •Loss of the nigrostriatal dopaminergic pathway (X) in PD upsets the fine balance of excitation and inhibition in the basal ganglia and reduces the _____ of motor cortex and its ability to generate commands for ____ movement, resulting in the poverty of movement. • Activity of direct pathway excites motor cortex • Activity of indirect pathway inhibit motor cortex • Dopamine ?? o Parkinson's- the input from the ___ ____ is lost Excited of motor cortex is also reduced Constantly inhibited by _____ pathway and not enough excitation to initiate voluntary movement

• •SN activity excites the direct pathway and inhibits the indirect pathway. substantial nigria excitation indirect voluntary

_____ _____ (directly linked) • -Fast transmission -Effect is very brief (a few ms to tens of ms) • Ion channels, the channel opens and changes the membrane permeability and change response of post synaptic neuron •____ _______ (second-messenger mediated) • 7-transmembrane G protein coupled receptors (GPCRs) • --Effect is longer, can last minutes Effectors (AC,PLC) Second messengers (cAMP,Ca2+) Altered protein kinase/phosphatase activities Effects on other neural processes

•Ionotropic receptors Metabotropic receptors

Local Anesthetics _____ ________ are drugs used to prevent or relieve pain in specific regions of the body without loss of consciousness •Local anesthetics reversibly bind to voltage-gated Na+ channels, block ______ influx and thus block ___ ______ generation and ____ _____ If the Na gate is closed—propagation failure • ____ is not received

•Local anesthetics (LAs) Na+ action potential nerve conduction Pain

Parasympathetic division ________ - when there is perceived danger with no perceived escape there may be massive activation of the parasympathetic division • loss of control over ____ and ______ -____ ____ (cranial nerve X) contains • ~ ______ % of preganglionic parasympathetic fibers, transmits sensory information from internal organs to the brain and parasympathetic output from the brain to organs. • Most _____ _supply to most organs ____________________ •The ability to change the refractive power of the lens allows objects at different distances to be focused on the retina. •If a distant object moves toward the eye, the lens becomes more _____ to keep the object in focus. • Close by, lens ? •Changing the shape of lens to focus an object is called _______ .

•Paradoxical fear urination and defecation •Vagus nerve 75 parasympathetic Accommodation curved accommodation

Sarcoplasmic Reticulum: Skeletal Muscle ______ consists of longitudinal tubules, which release Ca 2+ ___ ______ enlarged regions at the end of the tubules that concentrate and secrete Ca2+ . __________ pass down into the muscle cell and go around the myofibrils, conduct impulses from the surface of the cell(sarcolemma) to SR. •One T tubule and its two flanking cisternae are called ____ . • Store and release _____ ions* main function • Initiate process of ____ ____

•SR terminal cisternae, •Transverse tubules (T tubules) atriad calcium muscle contraction

TRP (Transient Receptor Potential) channels _________ is activated by both noxious heat and capsaicin, the active ingredient of chilli peppers •TRPV1 is also modulated by low pH (a common consequence of inflammation) •TRPV1 receptors are also found in the ___ -___ -___ and are involved in the transmission and modulation of pain, integration of pain signals • High acidity - damaged or inflamed tissue

•TRPV1 central nervous system

KEY POINTS • _______ is the form of somatic sensation that detects noxious, potentially tissue-damaging stimuli. Pain has both a ______ somatic sensory component and an aversive _____ and _______ component. • _____ _______ express a set of channels, most notably transient receptor potential (TRP) channels, that are sensitive to noxious mechanical, thermal and chemical stimuli. These neurons also express receptors for ________ mediators and substances released by -_____ cells. • ________ is a clinically significant process in which nociceptors in an area extending beyond a tissue injury exhibit decreased thresholds for activation. Sensitization can be initiated by inflammatory mediators such as ________ . • NSAIDs act by _______ prostaglandin-mediated sensitization, specifically by inhibiting the enzyme -________ that is required for synthesis of prostaglandins from arachidonic acid. _____ drugs selectively suppress nociception, but not other sensory modalities, by binding to endogenous opioid receptors in descending analgesic pathways. • Damage to neurons in nociceptive pathways can lead to severe chronic pain syndromes, termed ___ ____

Nociception localizing emotional and motivational Peripheral nociceptors inflammatory damaged prostaglandins blocking cyclooxygenase Opioid drugs neuropathic pain.

_______ - Pain •The sensation of pain is initiated by _____ - free nerve endings that are stimulated by tissue damage • Fast pain induced an aversive behavioral response, while the slow pain more accurately conveys the full extent of the problem •A sudden, traumatic stimulus may arouse both types of pain in which the 'fast' sensation induces an aversive behavioral response, while the 'slow' sensation more accurately conveys the full extent of the problem. ___ ___ ______ responsible for transduction of painful stimuli express a large panoply of receptors and channels • Great variety of membrane receptors - to detect various types of chemical and mechanical stimuli ** slide 27 Slide 28* book Some stimulate G7 receptors

Nociception nociceptors Free nerve endings

&&&&&&&&&&&&&&&&&&& 36 ________________________________ •Most currently available traditional NSAIDs (aspirin, ibuprofen, naproxen) act by inhibiting cyclooxygenases (COXs), which convert lipid messenger arachidonic acid into prostaglandins •The majority of NSAIDs non-selectively inhibit both ___ and _____ •The inhibition of COX-1 is believed to be responsible for many of the unwanted_____ side effects of NSAIDs ____________ currently is the only COX-2 inhibitor licensed for use in the U.S. Nonspecific NSAIDs ______ Constitutive -all celsl o _______ —GI mucosal Protection o ________ - Hemostasis • COX 2: Inducible o ____________ Mediate pain, inflammation and fever • They inhibit each other, cause problems if used too often - increase risk of ulcer and bleeding • Want to create drug that stimulate _____ with no effect to COX 1 o Only one available—CELEBREX

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) COX-1 and COX-2 GI •Celecoxib (CELEBREX) Prostaglandins Thromboxane Prostaglandins COX 2

_____ is the cell's control center ____ _____ is a double membrane that separates the nucleus from the cytoplasm ______ - contains DNA that controls synthesis of ribosomal RNA ______ - is DNA and protein _____ _____: regulate movement of material into and out of the nucleus Nucleoli- synthesize RNA for arrival ???

Nucleus Nuclear Envelope- Nucleolus Chromatin Nuclear pores-

Nervous system terms • ____________ group or aggregation of neuron cell bodies in the central nervous system •________________ = group or aggregation of neuron cell bodies in the peripheral nervous system • __________= bundle of axons (surrounded by glia & connective tissue) in the PNS o No nerves in the ______ • _____________ = bundle of axons in the CNS (red arrow, CNS has glia, but no connective tissue) Nerves in CNS ______ are found • Only in the CNS In the PNS, components of the ______ division include • Sensory neurons Cell bodies of efferent neurons are located in • ________

Nucleus (pl. nuclei) = Ganglion (pl. ganglia) Nerve CNS Tract/Pathway Interneurons AFFERENT CNS

For each ATP Consumed During one cycle, the sodium-potassium pumps binds and moves • 3 Na+ ____ and 2K+ ___ The sodium potassium pump is a _________ protein • TRUE

OUT IN transmembrane

Glial Cells are found in the CNS contains (4)

Oligodendrocyes, Microgilia, Astrocytes, Ependymal cells

Neuroglia of CNS • _________- • Form myelin sheaths around axons in the CNS • One oligodendrocyte for many axons • Can myelinate ____ _____

Oligodendrocytes multiple axons

Demonstration of a graded potential in a pacinian corpuscle • _____ _______ is touch-pressure receptor in the skin, where mechanical energy is converted into electric signals. The electrical responses to an increasing pressure are shown. Graded potentials vary in amplitude (the larger the stimulus [stretch or pressure], the larger the depolarization).When the depolarization reaches the threshold, AP is generated in the sensory nerve.

Pacinian corpuscle

"Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage" International Association for the Study of Pain •____ is the most common symptom for which patient seek medical attention. According to the American Pain Society, prevalence of chronic pain in the United States is estimated to be _____ % or 105 million people •The sensation of pain alerts us to real or impeding tissue injury and triggers appropriate ____responses •Pain is a complex experience that involves not only the transduction of noxious environmental stimuli, but also cognitive and emotional processing by the brain

Pain 35.5

Pathways across the blood-brain barrier _____ _______ pathway o Water-soluble agents •_____ _____pathway o Lipid-soluble agents •____ ______ o Glucose, Amino acids ________________ o Insulin, transferrin o Endo and exo cytosis

Paracellular aqueous Transcellular lipophilic Transport proteins • Receptor-mediated transcytosis

____________ • 2nd most common neurodegenerative disease (after Alzheimer's disease) • - Mean onset = 57 years of age • - Affects _____ % of population over 60 years of age (1 to 1.5 million people in the United States alone) • • Disease progression is highly variable • • Can be early onset in some cases (juvenile parkinsonism, most likely genetically related)

Parkinson Disease (PD) 1-2

Membrane potential (mV) Time (milliseconds) Resting potential _______ : voltage-gated K+ channels open Hyperpolarization _______ : voltagegated Na+ channels open Threshold potential Na+ influx through ____ receptors Muscle Fiber Action Potential • Depolarization: voltagegated ____ channels open o Na+ influx through _______ receptor o K+ efflux

Repolarization Depolarization nicotinic receptors Na+ nicotinic

Inactivation of Neurotransmitters slide 62 • 1._____ into nerve terminals of ___ _____ by specific membrane transport systems transported into glial cells •____ inactivate neurotransmitters o Acetylcholine --- • Neurotransmitters can_____ out of the synaptic cleft •High-affinity membrane NE transporter (NET) terminates the actions of NE by______ •Once taken back up by the neuron, NE can be metabolized to inactive compounds by degradative enzyme ______ _____ or taken back up by the vesicle • ___ or _____

Reuptake glial cells Enzymes diffuse reuptake reuptake Reused or degraded

Ribosomes : RNA AND PROTEINS • ______ are small dense granules of RNA and protein that manufacture proteins under the direction of cell's DNA _______ : Site for targeted protein degradation proteolysis. • Enzymes that carry out such reactions are called _____ . • Get rid of unwanted things • Contains enzymes - called Proteases??

Ribosomes Proteasome proteases

Passive Transport • cell doesn't use energy 1. ____ _____ - directly across 2. _____ _____- with a help of transport proteins 3. ______ - diffusion of water • ____ to _____ concentration gradient • x________ the concentration gradient, no energy needed

SIMPLE Diffusion Facilitated Diffusion Osmosis High to low down

Neuroglia of PNS PNS: 1.____ ___ • Surround clusters of neuronal cell bodies in the PNS • Unknown function 2. ____ ____ • Form myelin sheaths around the larger nerve fibers in the PNS o Wrap around ____ • Vital to _____ _______

Satellite cells Schwann cells axons neuronal regeneration

******************************** Nodes of Ranvier- not myelinated ____ ____ action potential jumps from the Nodes of Ran Is the axon in the CNS or the PNS? • ___ Which do you think has a faster rate of AP conduction—myelinated or unmyelinated? • _____ Fast AP? Small or large diameter?

Schwann cell- PNS Myelineated

Extracellular matrix (EM) • _____ extracellular molecules • Provide ______ _____for the cells Two parts ____ ______ (collagen, elastic) _____ _____ • Highly hydrophilic o First and foremost function and _____ network of the cell

Secreted supporting network Protein fibers Ground substance supporting

______ : Contributes to tenderness, soreness, and hyperalgesia • After injury normally non-painful stimuli are able to produce pain as a result of _____ • Peripheral sensitization occurs when inflammatory mediators activate protein ______ , which phosphorylate TRP and sodium channels, resulting in decreased activation threshold; there is also increased synthesis and membrane insertion of chemically gated and voltage-gated ion channels => ______ (increased pain intensity in response to the same noxious stimulus: e.g. moderate pressure causes severe pain) • Release _____ _____ —bind to receptors which of present of membranes of noicereptor fibers o voltage gated ion channels ____ _____ occurs when activity generated by nociceptors during inflammation enhances the excitability of nerve cells in the spinal cord Sensitization • Peripheral and central pain sensitization --

Sensitization sensitization kinases hyperalgesia chemical mediators • Central sensitization

Divisions of the Nervous System ** slide 8 CNS (brain and spinal cord) PNC (cranial and spinal nerves) • ____ (afferent) o To CNS from ___ ___ • Motor (efferent) o From ___ to ____ Autonomic and sympathetic

Sensory biosensory organs CNS to organs

*************************************** Types of Receptors • A single cell has ______ types of receptors linked to various _____ _____ Extracellular Signal Molecules • Receptor- Channel ?? • Receptor-_____ o Enzyme incorporated • G Protein-coupled receptor Largest group o Seven transmembrane receptors ? o Interaction of the specific ___ ____ o Then they activate ____ _____ o Ex. Olfactory receptors Integrin Receptor o Changes cell cite cytoskeleton

multiple membrane proteins enzyme G protein signal transaction

KEY POINTS • Changes in membrane potential are brought about by triggering events that alter ____ _____ and_____ of ions across the membrane. • There are two kinds of potential change:_____ which serve as long distance signal and graded (local) potentials, which serve as____- -distance signals. • AP occurs in an all-or none fashion. If AP occurs, it is of the same______ , no matter how strong is the stimulus. • Graded potentials depend on the stimulus_____ , dissipate with_____ and can_____ , or add together. • The _____ ______ ensures a one-way signal propagation from the site of activation. Action potentials propagate most rapidly in_______ ,_____ diameter axons. • Electrical synapses are ____ _____ in which pores formed by____ allow ionic currents to move between cells. • Chemical synapses have three components: presynaptic terminal, postsynaptic membrane and synaptic cleft. • AP arriving at presynaptic terminal causes influx of ____ and_____ of NT which diffuses through synaptic cleft and binds to neurotransmitter receptors (can be two different types) at_____ membrane. • The effect of NT is turned off in three ways: (3). •_____ can modify various steps in synaptic transmission.

membrane permeability movement AP short magnitude strength distance summate refractory period myelinated large gap junctions connexons Ca2+ release postsynaptic\ Reuptake, enzymatic degradation, diffusion Drugs

• Action potential (AP) is a change in ____ _______ that occurs when voltage-gated ion channels in the membrane open, increasing the cell's permeability first to_____ and then to _____ o The influx (movement into the cell) of Na+ ______ the cell. The depolarization is followed by _____ efflux (movement out of the cell), which restores the cell to the resting membrane potential. o Opening of Na+ channels, depolarizes the membrane and cause an _____ At the peak of the AP • Sodium channels are ______ while gated potassium channels open During the falling phase of AP, the membrane repolarizes beyond the resting membrane voltage, the phenomenon is due to • A large number of open ______ channels - after hyperpolarization

membrane potential Na+ K+. * depolarizes K+ AP inactivated potassium

Intravenous Solutions • The term ____ _____ refers to a separation of charges across the membrane or to a difference in a relative number of___ and ___ in the ICF and ECF • intracellular compartment has a net ______ charge because there are some ___ ____ inside the cell which do not have matching cations. • extracellular fluid has a net positive charge: some ______ in the ECF do not have matching anions A cell placed in a hypertonic solution will • _____

membrane potential cations and anions negative protein anions cations Shrink

Fluid-Mosaic Model of Membrane • The mosaic disposition of _____ ____ and the fluid nature of the ____ _____ = fluid mosaic model • Not static, _____ -energy • Lipids and proteins move or float within membrane due to the _____ ____ • Degree of membrane fluidity depends on _______ and _____ ____ • Fluidity decreases with ____ _____ and _____ of tail ____ _____

membrane proteins lipid bilayer thermo thermal energy temperature and lipid content (lipid composition of membranes high cholesterol saturation fatty acids

Cerebrospinal fluid (CSF) • Three protective and nourishing membranes, meninges o 3 membranes are called _______ (3) _____________ • Stiff neck • Fever • Headache

meninges Dura mater Arachnoid mater Pia mater Meningitis

Energy stored in high-energy phosphate bonds is limited, so muscle fibers must use _______ to transfer energy from the chemical bonds of nutrients to ATP. •Studies show that even intense exercise uses only ____ % of ATP in a muscle fiber => fatigue comes from other changes in the exercising muscle. • Anaerobic glycolysis • Never can run out of ATP • We use only about 30% ATP in exercise

metabolism 30

•The ______ of the neuron function like train tracks and transport material up and down the ____-_______ transport •The movement of material is driven by ____ _____: kinesin powers _______ transport, dynein powers ______ transport. Cell Body to Axon Terminals called _______ Axon Terminals—>Cell Body called____ _____ *** 58

microtubules axon-axoplasmic motor proteins anterograde retrograde Anterograde transport Retrograde Transport

Cerebellum • Contains as many neurons as the rest of the brain • Receives a very large amount of input from_____ cortical areas as well as from the________ , vestibular, visual and auditory systems, ~1 million fibers • Consists of two major parts: o___________ (output structures) and ______ ______ * Cerebellar cortex has the intricate pattern of ____ and _____ • Recent evidence suggests that cerebellum might be also involved in certain cognitive processes.

motor somatosensory cerebellar deep nuclei cerebellar cortex cerebellar deep nuclei folds and fissures

Neuropathology of PD • The loss of SN neurons puts a brake on the output of ____ ____ inhibiting voluntary motor commands from descending to the brain stem and spinal cord. • As a result patients have difficulty initiating _____ movements (bradykinesia or akinesia), although involuntary, _____ movements can be normal.

motor cortex, voluntary reflexive

•Sequential activation of motor units to perform a designated task is called ____ _____ _____ -Weak stimuli activate motor neurons with _____ threshold -Increased stimuli recruit more motor units (neurons with higher thresholds start to fire) -As the stimulus increases even higher, motor neurons with the _____- thresholds begin to fire =>contraction approaches its maximum force

motor unit recruitment. lowest highest

• The basic unit of contraction in a skeletal muscle is ____ ____ • Motor unit is one _____ motor neuron and the muscle ____ it innervates. • When the motor neuron fires an AP,____ muscle fibers in motor unit contract. • Small motor units produce ____ movements

motor unit. somatic fibers all precise

Oligodendrocytes form ____ _____ _____ are modifed immune cells and act as scavengers

myelin sheeaths Microlglia