ANPS Exam 2

Channels, Receptors, Transmitters (pt. 3) Describe the properties of neurotransmitters.

"The chemical language of the nervous system" 4 "Rules" to be considered a neurotransmitter: 1. A neurotransmitter must be synthesized by & released from a neuron 2. The substance should be released from nerve terminals in a chemically or pharmacologically identifiable form 3. The substance should reproduce @ the postsynaptic cell the same events that are seen following presynaptic electrical stimulation 4. Appropriate mechanisms for termination of action must be present Can be EXCITATORY (causing depolarization of the membrane) or INHIBITORY (causing hyperpolarization of the membrane). See Figure 2.1

LECTURE 6: Skeletal Muscle Structure (pt. 1) List the major characteristics and functions of muscle tissue.

(Refer to Figure 6.1) Characteristics of Muscle Tissue: 1. EXCITABLE - ability to receive & respond to electrical stimulation 2. CONDUCTIVE - electrical signals can spread along membranes 3. CONTRACTILITY - ability to shorten forcibly when stimulated 4. EXTENSIBILITY - ability to extend & stretch 5. ELASTICITY - ability to recoil & resume resting length after stretch 5 Major Muscle Functions: 1. Produce movement 2. Maintain posture & body position 3. Protection 4. Maintain normal body temperature (muscle contraction = energy use = heat production) 5. Storage & movement of materials (sphincters) (Refer to Figure 6.2)

Graded Potentials & Action Potentials (pt. 4) Describe in detail the movement of ions during all the phases of the action potential.

1ST: Sodium entry through voltage gated sodium channels is responsible for the RISING PHASE of an AP. The rising (depolarizing) phase of an AP is a Positive Feedback Loop... - Positive Feedback Loop: response to a stimulus that causes a variable to change in the same direction as the initial change (depolarization causes more voltage gated Na+ channels to open increasing the depolarization, rapid rising phase of signal) 2ND: Potassium exit through voltage gated potassium channels is responsible for the FALLING (REPOLARIZING) phase of the AP The time needed to re-set voltage-gated Na+ channels to closed (ready) state creates Refractory Periods. Refer to Figure 4.2

Skeletal Muscle Structure (pt. 2) Describe the anatomy of skeletal muscle from the macroscopic to the microscopic level.

A skeletal muscle is composed of thousands of muscle cells, connective tissue, blood vessels & nerves... - Muscle CELLS (muscle FIBERS) are typically as long as the entire muscle. - Bundles of muscle fibers termed FASCICLES. - The EPIMYSIUM, PERIMYSIUM and ENDOMYSIUM are 3 concentric layers of CT proper... - These connective tissue layers provide protection, sites for blood vessel and nerve distribution, & are a means of attachment to the skeleton or other structures. - TENDONS are formed from collagen of endomysium, perimysium & epimysium - Fusion of embryonic MYOBLASTS results in multinucleated adult cells Under the light microscope, skeletal muscle fibers are MULTINUCLEATE and STRIATED (striped) appearance. Structural organization of the Skeletal MUSCLE FIBER... - 1 fiber = 1 cell - Within a cell: myofibrils = cytoskeletal rods SARCOLEMMA = Plasma membrane of a skeletal muscle cell SARCOPLASM = Cytoplasm of a skeletal muscle cell MUSCLE FIBER = 1 skeletal muscle cell Contents: - many nuclei located just inside sarcolemma - myofibrils = cylindrical rods packed into cell - mitochondria tucked in between myofibrils everywhere MYOFIBRIL: terms to know... MYOFIBRIL = 1 cylindrical rod within cell, built with myofilaments MYOFILAMENTS = thick and thin filaments & related proteins THIN FILAMENTS - actin plus related proteins THICK FILAMENTS - myosin & related proteins SARCOPLASMIC RETICULUM - network of membranes surrounding each myofibril TERMINAL CISTERNAE - dilations of SR filled w/ calcium T-TUBULES = TRANSVERSE TUBULES = invaginations of sarcolemma reaching to each myofibril (Refer to Figure 6.3)

The Synapse & Synaptic Transmission (pt. 2) Describe the basic steps required for synaptic transmission, and explain why calcium is a critical ion in this process.

Basic Steps of Neurotransmission: 1. AP arrives @ axon terminal. 2. Voltage-gated Ca2+ channels open and Ca2+ enters the axon terminal. 3. Ca2+ entry causes synaptic vesicles to release neurotransmitter by exocytosis. 4. Neurotransmitter diffuses across the synaptic cleft & binds to specific receptors on the postsynaptic membrane. 5. Binding of neurotransmitter opens ion channels, resulting in graded potentials. Chemically-gated channels on postsynaptic membrane. 6. Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. Refer to Figure 5.1 Importance of Calcium (Ca2+) in Synaptic Transmission: - Ca2+ entry into axon terminal is the critical step allowing for synaptic transmission - Vesicle fusion w/ plasma membrane is calcium-dependent - Ca2+ is tightly regulated within the neuron - Ca2+ is quickly removed from intracellular fluid by buffers, taken up by mitochondria, or ejected from the terminal by Ca2+ active transport pumps

LECTURE 3: The Resting Membrane Potential (pt. 1) Define the basic properties of bioelectricity (voltage, current and resistance) & the interrelationship between them explained by Ohm's Law.

CURRENT (I) - the flow of electrical charge measured in amperes (A) - in cells, charge is carried by ion movement RESISTANCE (R) - hindrance to charge flow by substances through which current must past measured in ohms - in cells, resistance comes from basic property of the plasma membrane - resistance is the inverse of permeability (more permeability = less resistance, less permeability = more resistance) VOLTAGE (POTENTIAL) - measure of potential energy generated by separated electrical charges measured in volts (V) - separation is most often a physical barrier (in cells, this is the plasma membrane) - in cells we refer to this as MEMBRANE POTENTIAL Bioelectricity is governed by OHM's LAW: Voltage = Current x Resistance (V = IR) - current is directly proportional to voltage (when ions move across a membrane, voltage changes) - current is inversely proportional to resistance

LECTURE 4: Graded Potentials & Action Potentials (pt. 1) Identify the functional regions of a neuron and relate to the distribution of specific ion channels in the membrane.

Distribution of Pumps and Channels in the Plasma Membrane of a Neuron: RECEPTIVE REGION: - Dendrites & Cell Body - Binding of neurotransmitter, generating graded potentials Includes: chemically gated cation channels, chemically gated K+ channels, chemically gated Cl- channels IMPULSE-GENERATING REGION: - Axon Hillock - Summation of graded potentials, initiation of action potential Includes: voltage-gated Na+ channels, voltage-gated K+ channels CONDUCTIVE REGION: - Axon - Propagation of action potentials Includes: voltage-gated Na+ channels, voltage-gated K+ channels SECRETORY REGION: - Axon terminals - Release of Neurotransmitters Includes: voltage-gated Ca2+ channels, Ca2+ pump ENTIRE NEURON: Includes: Na+/K+ pumps, Na+ leak channels, K+ leak channels Chemically-gated ion channels in receptive region underlie graded potentials. Type of ion moving at a synapse determines whether the graded potential is hyperpolarizing or depolarizing.

Nervous Tissue Overview (pt. 2) Describe the structural & functional organization of the nervous system.

Divided into structural & functional divisions (refer to Figure 1).

LECTURE 7: Neuromuscular Transmission and Muscle Contraction (pt. 1) Describe in detail the neuromuscular junction.

The NEUROMUSCULAR JUNCTION: The specialized synapse between motor neuron & skeletal muscle cell - Usually located mid-region of muscle fiber - 3 parts to identify: axon terminal of motor neuron, synaptic cleft (space), specialized region of muscle fiber called motor end MOTOR END PLATE: - specialized region of sarcolemma - numerous junctional folds to increase surface area at synapse - contains acetylcholine (ACh) receptors The NEUROMUSCULAR JUNCTION: The interaction between motor neuron & muscle cell - SOMATIC MOTOR NEURON = neuron synapsing on skeletal muscle - Axons branch extensively in skeletal muscle - 1 branch of a motor neuron will contact a single muscle fiber - ACETYLCHOLINE (ACh) is the only neurotransmitter used @ the Neuromuscular Junction

Neuromuscular Transmission and Muscle Contraction (pt. 5) Explain how sarcomere shortening causes muscle contraction.

Sliding Filament Model of Contraction: Sarcomere Shortening - results in sarcomere shortening into a contracted state - Z discs pulled closer together - thick & thin filaments do not change length: the amount of overlap changes - disappearance of H zone - narrowing or disappearance of I band

Nervous Tissue Overview (pt. 3) Identify & describe the microscopic anatomy common to all neurons.

2 main cell types: 1. NEURONS - Basic unit of the nervous system - Excitable cells that transmit electrical signals - Do not divide after developmental period 2. GLIA ("glue", aka NEUROGLIA) - "Non-excitable" - Primarily support & protect neurons (outnumber neurons ~10:1) - Undergo mitosis throughout life Distinguishing Features of Neurons: 1. EXCITABLE - the neuronal membrane generates electrical activity in response to a stimulation - neurotransmitters are the chemical signals which stimulate other neurons 2. CONDUCTIVE - electrical signals are propagated across the plasma membrane - signals may be local or self-propagating along the length of a neuron 3. EXTREME LONGEVITY - most neurons are formed before birth & are still present in advanced age 4. AMITOTIC - neurons lose their ability to divide - however, a few select regions display neurogenesis in the adult (hippocampus, olfactory bulb) All neurons share a basic microscopic anatomy (cytology) refer to Figure 1.2... The neuron CELL BODY is the biosynthetic center of the cell: - Biosynthetic center of cell (contains the nucleus & other organelles, site of protein synthesis) - Chromatophilic substance = NISSL BODIES (Nissl substance) (free & bound ribosomes, dark staining, grey color of grey matter) - Enclosed by plasma membrane & contains cytoplasm surrounding the nucleus - Conducts electrical signals toward the axon DENDRITES branch off the cell body & receive information from other neurons: - Dendron (Greek) - "tree" - Short processes branching off cell body ("dendritic tree", one or many) - DENDRITIC SPINE receive input & transfer to cell body - More dendrites/spines = more input Neurons can have simple or complex dendrite patterns ("arbors") The AXON is a singular process that transmits signals to other neurons: - Process emanating from cell body that communicates w/ other neurons, muscle cells, or glands - Variability in length AXON HILLOCK ("little hill") where axon leaves cell body - Numerous branches = AXON COLLATERALS that form axon terminals on multiple target cells - AXON TERMINALS form synapses w/ target cells (contain synaptic vesicles, site of neurotransmitter release) A SYNAPSE is made of a presynaptic neuron, the synaptic cleft & a postsynaptic neuron (refer to Figure 1.3) The CYTOSKELETON provides support & structure for neurons. - Microfilaments - Intermediate filaments - NEUROFILAMENTS (provide tensile strength throughout the neuron, bundle to form neurofibrils) - Microtubules

Nervous Tissue Overview (pt. 5) Identify & describe the different structural classes of neurons.

3 Different Anatomical Classes of Neurons: 1. MULTIPOLAR - many processes extend from the cell body; all are dendrites except for a single axon. 2. BIPOLAR - two processes extend from the cell body; 1 is a fused dendrite, the other is an axon. 3. UNIPOLAR/PSEUDOUNIPOLAR - 1 process extends from the cell body & forms central & peripheral processes, which together comprise an axon.

LECTURE 1: Nervous Tissue Overview (pt. 1) Describe the general functions of the nervous system.

3 General Functions: 1. Collect information = SENSORY INPUT - monitor changes in internal & external environment 2. Integration - interpret sensory input & determine proper response 3. Motor Output - activate effectors including muscle & glands

Neuromuscular Transmission and Muscle Contraction (pt. 2) Describe cellular and molecular events during the 3 phases of muscle contraction.

3 Phases of Muscle Contraction 1. NEUROMUSCULAR JUNCTION STIMULATION by Transmitter Release @ synapse 2. Excitation-Contraction Coupling: depolarization of the muscle cell leads to activation of sarcomeres 3. Crossbridge Cycling as actin & myosin repeatedly bind & release ... PHASE I: Neuromuscular Junction Stimulation - The neuromuscular junction is a specialized synapse - The neurotransmitter is ALWAYS acetylcholine - Acetylcholine is ALWAYS EXCITATORY at the NMJ - Junctional folds have Acetylcholine receptors, which are inotropic receptors that open to let both NA+ and K+ cross the membrane (cation channel) - Junctional folds have the enzyme acetylcholinesterase to quickly break down acetylcholine (Refer to Figure 7.1) .... PHASE II: Excitation-Contraction Coupling - Sequence of events by which stimulation of the muscle cell leads to AP formation & conduction along the sarcolemma (excitation) & then to sliding of the myofilaments (contraction) STEP 1: Development of an end-plate potential (EPP) @ the motor end plate STEP 2: Initiation & propagation of an AP along the sarcolemma & T-tubules STEP 3: Release of Ca2+ from the sarcoplasmic reticulum (Refer to Figure 7.2) .... PHASE III: Sarcomere Cross Bridge Cycling - Consistes of 4 repeating steps: 1. Cross bridge formation - energized myosin head attaches to an actin myofilament, forming a cross bridge 2. Power stroke - ADP & Pi are released & the myosin head pivots & bends, changing to its bent low-energy state. As a result it pulls the actin filament toward the M line. 3. Cross bridge detachment - after ATP attaches to myosin, the link between myosin & actin weakens, & the myosin head detaches (the cross bridge "breaks") 4. Cocking of the myosin head - as ATP is hydrolyzed to ADP and Pi, the myosin head returns to its prestroke high-energy, or "cocked" position - Results in sarcomere shortening into a contracted state - Continues as long as ATP is available and Ca2+ present (Refer to Figure 7.5)

The Resting Membrane Potential (pt. 4) Describe how neurons establish & maintain resting membrane potential.

3 membrane properties critical for establishing membrane potential: 1. MECHANICAL BARRIER - separates two of the body's fluid compartments 2. SELECTIVE PERMEABILITY - determines manor in which substances enter or exit cell 3. ELECTROCHEMICAL GRADIENT - ions want to achieve both chemical & electrical equilibrium & will move rapidly when allowed to These properties allow cells to generate an ionic imbalance across the membrane creating a membrane potential, or voltage across the membrane. - All human cells are said to be polarized at rest (Neurons -60mV, Muscle -90mV, red blood cells -7mV) - When the cell is @ rest this potential is called the RESTING MEMBRANE POTENTIAL (RMP). Resting Membrane Potential (RMP) is generated by ionic concentration gradients & active transport - Ionic concentration gradients ESTABLISH resting membrane potential - Primary Active Transport MAINTAINS resting membrane potential Diffusion of POTASSIUM through leak channels is the key to ESTABLISHING the RMP. If a cell only had K+ leakage channels, it would have a RMP of -90 millivolts (mV). Add in a few Na+ leakage channels, its RMP is -70. +60 if it only had Na+ leakage channels. Sodium always wants to come in, potassium always wants to leak out. Changing the Membrane Potential: Graded Potentials - Localized changes in membrane potential - Results in depolarization OR hyperpolarization (dependent on neurotransmitter release & chemically-gated ion channels present in plasma membrane) - Less separation of charge as we move towards 0; DEPOLARIZATION & HYPERPOLARIZATION are relative. The cell is at rest when we are looking at the effects of the leakage channels. Na+/K+ ATPase (pump) MAINTAINS RMP by restoring ionic imbalance - Rate of the pump activity will depend on the influx of Na+ - Without this pump both the RMP & osmotic balance would be disrupted - Pump activity allows cells to experience large changes in membrane potential without long-term damage Refer to Figures 3.3 & 3.4

Graded Potentials & Action Potentials (pt. 6) Contrast graded potentials and action potentials.

Changes in resting membrane potential can produce two types of signals: GRADED POTENTIALS - incoming signals operating over small distances (refer to Figure 4.1) ACTION POTENTIALS - long-distance signals of axons GRADED POTENTIALS: - "Graded" means they are variable in amplitude (size) - Size dependent on stimulus magnitude (larger stimulus will open more chemically gated channels increasing net ionic movement) - Spread away from site of origin and decrease in intensity as they spread in distance from site of origin - Short-lived: potential lasts until local ion current ceases - Occur at postsynaptic side of synapse in response to stimulation by neurotransmitter opening chemically (ligand) gated ion channels ("POSTSYNAPTIC POTENTIAL") The ACTION POTENTIAL (AP): - Principal mechanism neurons use to communicate over long distance (generation & propagation) - Only seen in cells with excitable membranes (neurons & muscle) - Graded potentials trigger action potentials at the axon hillock in a multipolar neuron - Dependent on reaching a "threshold value" - "all or none" event - Involves temporary reversal of polarity across plasma membrane (~100 mV reversal) (depolarization to re-polarization to hyperpolarization to RMP, has a characteristic shape determined by activity of voltage gated channels (Na+ and K+)) - No decay with distance (self-propagating down axon) Changing the Resting Membrane Potential: Depolarization & Hyperpolarization: DEPOLARIZATION - the membrane potential moves toward 0 mV, the inside becoming less negative (more positive) HYPERPOLARIZATION - the membrane potential increases, the inside becoming more negative

The Resting Membrane Potential (pt. 2) Describe the relationship between intracellular & extracellular ion concentrations for the major ions sodium, potassium, chloride & calcium.

Creation of a Membrane Potential in an Artificial System: START INSIDE the cell: - High potassium = major cation - Intracellular proteins = major anion OUTSIDE the cell: - High sodium = major cation - High chloride= major anion At start: cell & solution are electrically neutral = same number of + & - charges on each side of membrane. - Cell has no membrane potential - System is in electrical equilibrium - System is in chemical disequilibrium w/ strong chemical gradients STEP 1: Add potassium leakage channels - LEAK CHANNELS ARE ALWAYS OPEN - Potassium leak channels provide SELECTIVE PERMEABILITY - only potassium passes through - Potassium moves by simple diffusion by its concentration gradient - Transfer of one K+ results in a electrical disequilibrium establishing an ELECTRICAL GRADIENT - Cell now has membrane potential (inside of the cell is negative relative to the outside)

LECTURE 5: The Synapse & Synaptic Transmission (pt. 1) Identify and describe in detail the structure and function of the chemical synapse, and contrast with an electrical synapse.

ELECTRICAL SYNAPSE: - Uncommon in humans - Signaling through Gap Junctions - No synaptic delay; very fast CHEMICAL SYNAPSE: - Most common synapse in humans - Synaptic Delay (slower; time for transmission across the synaptic cleft - the rate limiting step in transmission)

The Synapse & Synaptic Transmission (pt. 3) Define and describe an EPSP and an IPSP.

Excitatory Postsynaptic Potential (EPSP) Sequence of events: 1. Excitatory neurotransmitter crosses synaptic cleft, binds to a receptor, and opens a chemically gated cation channel. 2. Na+ moves into neuron through the open channel. 3. Inside becomes slightly more positive (depolarized). This positive (less negative) state is called EPSP. Brings neuron closer to AP threshold. 4. EPSPs will travel toward the axon hillock of postsynaptic neuron (decreases in amplitude w/ distance traveled). Inhibitory Postsynaptic Potential (IPSP) Sequence of events: 1. Inhibitory neurotransmitter cross synaptic cleft, binds to chemically gated K+ channel or Cl- channel. Depends on neurotransmitter and channels present (if neurotransmitter opens K+ channel, K+ moves out of neuron; if neurotransmitter opens Cl- channel, Cl- flows into neuron). 2. Inside of the cell becomes slightly more negative, this negative state is the IPSP. IPSPs bring neuron farther away from the AP threshold. 3. IPSPs will travel passively toward the axon hillock of postsynaptic neuron (graded potential, so decreases in amplitude w/ distance traveled).

Nervous Tissue Overview (pt. 7) Compare & contrast the structure & function of different glial cells in the central & peripheral nervous system.

GLIAL CELLS: - "Non-excitable" - Support, protect & provide scaffold for neurons - Outnumber neurons 10:1 (about half the mass of the brain) - Mitotic CNS Glial Cells: ASTROCYTES - Most abundant glial cell in the CNS - Astrocyte END FEET cover capillaries (regulate nutrients to neurons, blood-brain barrier) - Control chemical environment around neurons (potassium ion buffering, neurotransmitter uptake/metabolism) CNS Glial Cells: OLIGODENDROCYTES - highly branched from a single soma - wrap processes tightly around axons producing an insulted lipid membrane covering (myelin sheath) - can support axons of many surrounding neurons CNS Glial Cells: MICROGLIA & EPENDYMAL CELLS Microglia: - small ovoid w/ many long 'thorny' processes - monitor neurons & extracellular space for health & signs of disrupted homeostasis - transform into type of macrophage - capable of phagocytosis Ependymal Cells: - range from squamous to columnar w/ cilia - line CNS fluid-filled cavities - produce cerebrospinal fluid (CSF) - cilia help circulate CSF PNS Glial Cells: SATELLITE CELLS & SCHWANN CELLS Satellite cells: - surround ganglion neuron cell body - regulate cellular environment similar to astrocytes in the CNS Schwann cells: - myelinate PNS axons - similar to oligodendrocytes - critical for nerve regeneration Large axons in the CNS & PNS are MYELINATED. The role of myelin: - Insulates & protects axon - Speeds conduction of electrical impulses down axon (more on this later) Schwann Cells myelinate axons in the PNS: - Schwann cells myelinate INTERNODE of single axon - Takes many to myelinate entire axon Gap between segments of myelin (NODE OF RANVIER) Oligodendrocytes myelinate axons in the CNS: - Oligodendrocytes myelinate 1 mm region (internode) of many axons - Processes wrap around axons - Gap between Myelin sheath (Node of Ranvier) Axons are either myelinated or ensheathed. MYELINATED: few to many layers of lipid membrane wrapping. ENSHEATHED: axons isolated from one another but no layers of lipid. PNS Structures: NERVE & a DORSAL ROOT GANGLION Nerve - cable like bundle of parallel axons w/ their glia in the peripheral nervous system. Ganglion - cluster of neuron cell bodies in the peripheral nervous system.

The Synapse & Synaptic Transmission (pt. 5) Describe and contrast global synaptic inhibition with selective synaptic inhibition.

GLOBAL PRESYNAPTIC INHIBITION prevents a neuron from signaling any of its target cells. - Terminals do not get AP, transmission inhibited for the whole neuron. - If a neuron fails to generate an AP, there is no signal to conduct down the axon and no neurotransmitter will be released at any of its terminals. (Refer to Figure 5.4) SELECTIVE PRESYNAPTIC INHIBITION inhibits release of neurotransmitter from only some axon terminals. - Positive inputs coming into the cell, conduct AP, goes down the axon... - Very selective. - Neuron generates action potential and conducts it down axon toward terminals. - Inhibition at individual terminals will prevent their transmitter release; remaining terminals of that neuron will release transmitter. (Refer to Figure 5.5)

LECTURE 2: Channels, Receptors, Transmitters (pt. 1) Contrast ion channels with receptors.

ION CHANNEL: an integral membrane protein that allows ions to pass between intracellular & extracellular environments - Leak ion channels - Gated ion channels RECEPTOR: an integral membrane protein that produces a physiological change in a cell after a LIGAND (signaling molecule) binds Classes of Receptors: IONOTROPIC RECEPTORS: ion channels that open or close in response to an extracellular signal; open ion channels allow ions to move & carry across the membrane METABOTROPIC RECEPTORS: are membrane proteins that respond to an extracellular signal by altering the metabolism in the cell An ion channel can be a type of receptor, but not all receptors are ion channels. Ion channels have pores that are selective for specific ions - SELECTIVE PERMEABILITY. - Ions cannot cross the phospholipid portion of the membrane; Ion channels are integral membrane proteins w/ a central PORE region - Ion channel pores are selective; SELECTIVITY regulates the passage of ions based on size & charge Ion Channel pores may be leakage channels or gated channels...

Neuromuscular Transmission and Muscle Contraction (pt. 3) Explain why calcium is important for skeletal muscle contraction.

In a skeletal muscle cell, depolarization of the t-tublue membrane triggers opening of Ca2+ channels of the terminal cisternae & release of calcium into the sarcoplasm of the muscle cell. - The rise in Ca2+ triggers CONTRACTION. (Refer to Figure 7.3)

Channels, Receptors, Transmitters (pt. 2) Contrast leakage ion channels with ligand gated & voltage gated ion channels.

LEAKAGE CHANNELS are ion channels that are always open. - Establish resting membrane potential - Leak channels are selective for a specific ion, but do not display gating or respond to stimuli GATED ION CHANNELS open & close. - Allow ion movement only when open - Control PERMEABILITY for an ion - Open channels allow passive movement of ions down their chemical & electrical gradient while the channel is open GATED ION CHANNELS open & close by physical changes to their protein structure & in response to different stimuli... VOLTAGE GATED: - Open in response to a key CHANGE in membrane voltage - Highly concentrated in muscle & nerve tissue EX. voltage gated Na+ channel, voltage gated K+ channel CHEMICALLY (LIGAND) GATED: - Open in response to binding of an extracellular signal; open following binding of a SPECIFIC chemical - Many neurotransmitters will work via this mechanism

Skeletal Muscle Structure (pt. 4) Identify the different regions of the sarcomere and explain how the shape of the sarcomere changes during contraction.

MYOFIBRILS consist of repeating units called SARCOMERES. The SARCOMERE is the functional unit of skeletal muscle contraction, and is organized into anatomically & physiologically distinct regions... A band (DARK regions): - central region of sarcomere - contains entire thick filament - contains partially overlapping thin filaments - appears dark under a microscope I bands (LIGHT regions): - contains only thin filaments - extend from both directions of Z disc - appear light under a microscope - disappear @ maximal muscle contraction Z discs: - contains specialized proteins running perpendicular to myofilaments which anchor thin filaments M line: - protein meshwork structure @ center of H zone - attachment site for thick filaments H zone: - central portion of A band - only thick filaments present; no thin filaments - disappears during maximal muscle contraction

Nervous Tissue Overview (pt. 6) Describe the anatomical organization of nerves & synapses.

Neurons can be divided into 4 functional regions: 1. RECEPTIVE REGION - cell body & 2. IMPULSE-GENERATING REGION - axon hillock/trigger zone 3. CONDUCTING REGION - axon 4. SECRETORY REGION - terminal

Channels, Receptors, Transmitters (pt. 4) Name the classes of neurotransmitters, & name a transmitter within each class.

Neurotransmitters are classified into major groups based on chemical structure. Neurons typically synthesize & release 1 or 2 neurotransmitters, & are named for the dominant transmitter released (i.e., cholinergic, adrenergic, dopaminergic). Neurotransmitters, ACETYLCHOLINE (ACh): - Synthesized in the presynaptic terminal from choline (from diet) & acetyl coenzyme A (CoA) - ACh is released from all somatic motor neurons, many neurons of the ANS, & many CNS neurons - Broken down (degraded) in the synapse by the enzyme ACETYLCHOLINESTERASE Neurotransmitters, BIOGENIC AMINES: - Synthesized in the cell from single amino acids (MONOAMINES) - Removed from synapses by selective uptake or "REUPTAKE"(transported back into nerve terminal, target cell, or astrocytes) - Catecholamines: closely related chemically (DOPAMINE, NOREPINEPHRINE, EPINEPHRINE) - Indolamines: SEROTONIN (5-HT) Neurotransmitters, Other Classes: AMINO ACIDS: - Glutamate (generally excitatory - principal excitatory neurotransmitter in the brain) - GABA (generally inhibitory - principal inhibitory neurotransmitter in the brain) - Glycine (inhibitory - major inhibitory neurotransmitter in the spinal cord & brain stem) NEUROPEPTIDES (small proteins made in the rER/Golgi @ cell body): - Substance P - Endorphins (Endogenous Opiates) ENDOCANNABINOIDS: - lipid based GASEOUS: - Nitric Oxide See Figure 2.2

Graded Potentials & Action Potentials (pt. 7) Describe action potential propagation from the soma to the axon terminal and contrast continuous and saltatory conduction.

Once an Action Potential is generated it must be PROPAGATED down the axon. 1. action potential 1st generated in axon hillock 2. action potential propagated down axon to every axon terminal Voltage-gated sodium and voltage-gated potassium channels are found from the axon hillock to the axon terminal and allow conduction of action potential to terminal. The action potential travels as a "wave" of ionic current down the axon membrane. Action potentials do not propagate backwards because voltage-gated Na+ channels transition to the inactivated state after opening (absolute refractory period). CONTINUOUS CONDUCTION: - Occurs in unmyelinated axons - Sequential opening of voltage-gated Na+ and K+ channels at every point along the length of the axon - Slow SALTATORY CONDUCTION: - Occurs in myelinated axons - Nodes have bare membrane where ions can cross membrane - Action potentials generated only at nodes of Ranvier with large numbers of voltage-gated Na+ and K+ channels - Myelinated regions are well insulated electrically, so current doesn't leak out of axon Factors influencing velocity of propagation = CONDUCTION VELOCITY 1. Diameter of axon: - larger diameter, faster the velocity of the signal 2. Myelination of axon: - more important factor - thicker myelin sheath = faster the velocity of the signal - AP only regenerates at the Nodes of Ranvier - diseases affecting myelin sheath alter signal conduction unmyelinated - AP must be regenerated at every point along the length of axon myelinated - AP is regenerated only at nodes of Ranvier

Neuromuscular Transmission and Muscle Contraction (pt. 4) Describe in detail the 4 stages of cross bridge cycling.

Refer to Figure 7.4

Skeletal Muscle Structure (pt. 3) Describe thick and thin filaments, what are they composed of and how they interact w/ each other.

SARCOMERES are composed of THICK and THIN FILAMENTS... THICK FILAMENTS are composed of MYOSIN molecules. THICK FILAMENTS: - assembled from bundles of protein molecules called MYOSIN - each myosin molecule has 2 intertwined strands (tails) and 2 globular heads - in the filament, tails point toward center of thick filament (center of sarcomere) - heads stick out from filament on all sides - each head has special BINDING SITES (1 for actin of thin filaments, 1 for ATP which will be split by ATPase region of myosin protein) THIN FILAMENTS are composed of ACTIN molecules w/ 2 regulatory molecules: THIN FILAMENTS: - composed primarily of 2 strands of actin - strands twisted around one another - actin strands composed of spherical molecules, globular actin (G-actin) - connect to form a fibrous strand, filamentous actin (F-actin) - actin subunits have a myosin binding site, where myosin head attaches during contraction TROPOMYOSIN: - twisted string-like protein - covers small bands of F-actin - covers myosin binding sites in non-contracting muscle TROPONIN: - globular protein attached to tropomyosin - has binding site for Ca2+ - Calcium sensor! - together form troponin-tropomyosin

The Resting Membrane Potential (pt. 3) Describe electrochemical gradients (driving force) & equilibrium potentials, & explain why they are important in normal cell function.

STEP 2: Formation of an ELECTROCHEMICAL GRADIENT - Electrical & chemical gradients begin an ionic "tug of war" w/ ions creating an ELECTROCHEMICAL GRADIENT ELECTROCHEMICAL EQUILIBRIUM occurs when electrical gradient in one direction is balanced by & chemical gradient in the other direction. - For any given concentration (chemical) gradient across a membrane there is an electrical gradient that directly opposes ion movement down that concentration gradient - When chemical & electrical gradient forces are equal the cell is at the equilibrium potential (Eion) Electrochemical gradients are based on intracellular & extracellular ion concentration IMPORTANT: Na+ & Cl- leaving being pushed into the cell, K+ being pushed out. Ca++ also being pushed into the cell. - Electrochemical gradients can also be described as a "driving force" (the force that creates a tendency for ions to move) Refer to Figures 3.1 & 3.2

The Synapse & Synaptic Transmission (pt. 4) Describe and define temporal and spatial summation.

SUMMATION: the signal we measure in the cell is the sum of all the signals generated by all the synapses active at 1 time. TEMPORAL SUMMATION of Graded Potentials: - Repeated release of excitatory neurotransmitter @ same location - Effects added together if occur within small timeframe - AP initiated only if combined EPSPs lead to threshold at axon hillock (Refer to Figure 5.2) SPATIAL SUMMATION of Graded Potentials: - Release of neurotransmitter from multiple presynaptic neurons - AP initiated if net effect of the postsynaptic potentials brings axon hillock to threshold - Can also prevent an AP from being generated (Refer to Figure 5.3) SYNAPSE LOCATION MATTERS. EPSPS and IPSPs are graded potentials that decay w/ time & distance. Those closer to trigger zones/axon hillocks will have more impact.

Graded Potentials & Action Potentials (pt. 5) Explain the 'all or none' principal for an action potential.

The Action Potential (AP) is an ALL OR NOTHING event. - If threshold is reached, an AP is generated - If threshold is not reached, an action potential is not generated - Action potentials are always the same, they do not get bigger w/ greater depolarization (a threshold stimulus creates the same AP as a suprathreshold stimulus - Similar to firing a gun

Graded Potentials & Action Potentials (pt. 3) Explain the concept of action potential 'threshold'.

THRESHOLD voltage must be reached to generate an action potential. Neurons have a critical depolarization value called THRESHOLD (usually between -50 and -55 mV) at which depolarization becomes self-generating and action potentials initiate. - A high concentration of voltage-gated Na+ channels at the axon hillock facilitates the generation of action potentials. Any depolarization value not reaching threshold is a subthreshold value and no action potential is generated. A depolarization value above threshold is called suprathreshold, but does not generate a bigger action potential.

Nervous Tissue Overview (pt. 4) Define & describe axonal transport.

The cell body communicates w/ the axon terminal via AXONAL TRANSPORT. Axons depend on bidirectional axon transport. 1. ANTEROGRADE TRANSPORT: movement of materials from cell body to synaptic terminals (basically forward; shipped from the cell body down towards the terminal) - new membrane, mitochondria, enzymes, vesicles 2. RETROGRADE TRANSPORT: movement of materials from synaptic terminals to cell body - carries organelles back for recycling, carries back information (via signaling molecules) 2 Types of Transport within Axon: SLOW AXONAL TRANSPORT: - Occurs at about 0.1 to 3 mm/day - Substances only moved from cell body towards terminal (anterograde transport) (enzymes, cytoskeletal components, new axoplasm) FAST AXONAL TRANSPORT: - Occurs at about 400 mm per day - Involves movement along microtubules - Specialized motor proteins hydrolyze ATP (energy dependent) - Anterograde or retrograde motion possible (anterograde transport of vesicles, organelles, glycoproteins) (retrograde transport of used vesicles, potentially harmful agents)

Graded Potentials & Action Potentials (pt. 2) Describe in detail the properties of the voltage-gated sodium and potassium channels.

Voltage-gated Na+ Channels transition between 3 conformational states: closed, opened, inactivated - Selective for sodium ion only 2 separate ion channel gates: 1. Voltage-sensitive ACTIVATION GATE that is closed at rest and opens following depolarization 2. INACTIVATION GATE that closes shortly after channel opens Voltage-gated K+ Channels: - Selective for potassium ion only - Voltage-sensitive gate that is closed at rest and opens following depolarization - 2 states, open or closed - Opening delayed compared to voltage gated Na+ channel