Detailed Learning Objectives

Using table 5.1, describe the difference between an agonist versus an antagonist.

Agonist: a chemical messenger that binds to a receptor and triggers the cell's response; often refers to a drug that mimics a normal messenger's action; some decongestants are examples of agonists; TRIGGERS SUBSEQUENT EVENTS Antagonist: a molecule that competes with a ligand for binding to its receptor, but does NOT activate signaling normally associated with the natural ligand; therefore, an antagonist prevents the actions of the natural ligand; PREVENTS SUBSEQUENT EVENTS EX: certain types of antihistamines

Describe and illustrate the calcium-dependent exocytosis of neurotransmitter via the SNARES and fusion pores.

- Ca2+ binds synaptotagmin, which is a SNARE PROTEIN (Ca2+ sensor), and this causes the SNARE complex to draw the vesicle to the plasma membrane - These protein complexes increase fusion rate MANY fold

Using figure 6.27 as a guide, list the presynaptic events involved in neurotransmitter release at chemical synapses.

1. Action potential propagates to termina 2. Ca2+ channels open (voltage-gated channels) and Ca2+ enters the axon terminal 3. Ca2+ activates vesicle exocytosis (vesicles in axon terminal contain neurotransmitter) 4. Neurotransmitter diffuses across tiny gap (15 nm)

List our four general types of carrier-mediated transport. Using figure 4.10, discuss the principle features of the four general types of carrier-mediated transport. What do they have in common and what makes them unique?

1. Facilitated diffusion - moves in direction of conc. gradient 2. Primary active transport - against conc. gradient; needs energy source; energy source: ATP hydrolysis 3. Secondary active transport - against conc. gradient; needs energy source 4. Channel-mediated diffusion

State four functions of a plasma membrane (see Table 3.1).

1. Regulates passage of substances into and out of cells and between organelles and cytosol (selective permeability) 2. Detect chemical messengers arriving at surface (receptors) 3. Anchor cells to extracellular matrix (desmosomes and gap junction) 4. ?

Explain the concept of a "set point" in physiology and discuss an example of when a set point might change.

A set point is a value that represents the steady state of a physiological variable and a value that is maintained through homeostasis (think of how 98.6 degrees Fahrenheit is a "normal" body temperature). All homeostatic systems work around a set point. Ex: A set point might change if you have a fever

Describe what is meant by sensory stimulus transduction and define an adequate stimulus.

Adequate stimulus: what a receptor typically responds to and what it is most sensitive to

Using figure 4.8, draw and describe facilitated diffusion.

Facilitated diffusion: large, polar, hydrophilic solutes; down a conc. gradient (either way across membrane), no energy needed in form of ATP hydrolysis (energy source: chemical conc. gradient); has binding site for solute

Sketch figure 6.38 and identify the forebrain (and its parts), the brainstem (and its parts), and the cerebellum.

Forebrain: cerebrum, diencephalon, thalamus, hypothalamus Brainstem: midbrain, pons, medulla oblongata Cerebellum

Draw and discuss figure 6.16 to illustrate key characteristics of graded potentials.

Graded potentials come first and can lead to action potentials; dendritic regions are where graded potentials occur - Graded potentials are proportional to the size of the stimulus - Decrease with distance from the stimulus site - Can be depolarizations OR hyperpolarizations - Can SUMMATE with each other (their amplitudes add up together) - They are short-distance signals that rely only on the local flow of ionic currents - They are also known as "generator potentials and "sensory receptor potentials"

Draw, label, and discuss figure 6.15 to demonstrate your understanding of a graded potential.

Graded potentials come first and can lead to action potentials; dendritic regions are where graded potentials occur - Graded potentials are proportional to the size of the stimulus - Decrease with distance from the stimulus site - Can be depolarizations OR hyperpolarizations - Can SUMMATE with each other (their amplitudes add up together) - They are short-distance signals that rely only on the local flow of ionic currents - They are also known as "generator potentials and "sensory receptor potentials"

Using figure 4.9 and your lecture notes, discuss two experiments that measure solute flux rates and reveal the difference in saturation behavior between diffusion and carrier-mediated transport.

In diffusion, flux rate is limited by conc. gradient, permeability, surface area (Fick's Law). In carrier-mediated transport, the number of available carriers places an upper limit on the flux rate. In carrier-mediated transportation processes, saturation occurs. In diffusion, saturation does NOT occur (ion diffusion through channels can saturate at non-physiologic conditions, like ridiculous conditions that you wouldn't find in a human body)

Draw figure 5.6 and describe the steps of the PKA signal transduction cascade. Then draw figure 5.9 and provide some example targets/responses to activated PKA.

PKA CASCADE: - Start off with hydrophilic messenger that binds to a metabotropic receptor (receptor that is connected to a cascade) - Associated to this receptor is a G protein (Gs protein) - G proteins connect the metabotropic receptor to an effector - Gs protein activates an enzyme called adenylyl cyclase - Now, we convert ATP into a molecule called cAMP - cAMP is the second messenger (inside cell) - cAMP activates a kinase called PKA (protein kinase A) - Kinases phosphorylate protein - This phosphorylated protein will give rise to the cell response EX of what PKA can do: when our Na+/K+ pump is phosphorylated, it runs faster; ion channels can be phosphorylated if you want them to move more or less ions; alter organelle function; alter DNA transcription; regulate metabolic processes

Using figure 4.19 explain what would happen to the volume of a cell dunked into a solution that is: isotonic, hypertonic, and hypotonic.

** REMEMBER: in a cell's intracellular fluid, there is 300 mOsm of NP solutes (can't cross the membrane). The following terms describe the ECF, not the ICF ** ** Tonicity: only considers the non-penetrating solutes ** Isotonic: If our cell is placed in a solution with 300 mOsm of NP solutes, nothing will happen - isotonic solution (no change in cell volume) - but remember, simple diffusion is still occuring! (no net diffusion) Hypertonic: If our cell is placed in a solution with 400 mOsm of NP solutes, water will leave the cell - hypertonic solution (the cell will shrink) Hypotonic: If our cell is placed in a solution with 200 mOsm of NP solutes, water will enter the cell - hypotonic solution (cell swell)

List the postsynaptic events that underlie excitatory postsynaptic potentials (EPSPs).

*** Depolarizing the membrane *** - Neurotransmitter binds to the receptor - Ligand-gated channels open (chemical-gating) - THIS IS AN IONOTROPIC RECEPTOR - Cations flow through Na+ or Ca2+ - Net effect is depolarization (a tiny EPSP)

Draw figure 6.33 and define both presynaptic inhibition and presynaptic facilitation.

*** Monarch (pre-synaptic) vs. minions (post-synaptic) and the advisor to the monarch is the axo-axonic synapse *** Presynaptic facilitation: - Increases neurotransmitter release from PreB to PreC - Thus, it can facilitate both excitatory and inhibitory synapses - "A" increases from PreB to PostC Presynaptic inhibition: - Decreases neurotransmitter release from PreB to PostC - Thus, it can inhibit both excitatory and inhibitory synapses - A decreases from PreB to PostC

List the postsynaptic events that underlie inhibitory postsynaptic potentials (IPSPs).

*** Reduce AP probability of occuring *** - Neurotransmitter binds to receptor - Ligand-gated channels open (chemical-gating) - Either K+ flux out or Cl- flux in (Cl- is ALWAYS INHIBITORY)

Draw a simplified body plan as we did in lecture. Differentiate between the external and internal environments. Include all the talking points presented during lecture.

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Draw an example graph that illustrates summation of graded potentials.

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Per figures 3.5 and 3.6, draw a typical plasma membrane and its molecular components.

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Reproduce the diagram we developed in class that explains the concept of an electrochemical gradient and how its components affect the movement of an ion through a cell membrane.

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Sketch and describe the anatomy of an afferent neuron, detailing which portions are in the peripheral nervous system and which are in the central nervous system.

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Use figure 6.26b to sketch chemical synaptic transmission that occurs axo-dendritic, axo-somatic, and axo-axonic. For all three, label pre and post-synaptic membranes, the synaptic cleft, the vesicles with neurotransmitter before exocytosis, and the net diffusion of neurotransmitter across the cleft.

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Using figure 6.14, define and discuss what is implied by depolarization, overshoot, repolarization, and hyperpolarization.

- A cell is "polarized" because its interior is more negative than its exterior - If membrane potential goes from -70 mV towards 0 mV, it is becoming LESS polarized (depolarization) - Occurs when ion movement reduces the charge imbalances - If we go past 0 mV into positive membrane potentials, we call this overshoot - When we return towards rest, we call this repolarization - For repolarization, it does NOT matter where you start for rest! - If you go below -70 mV, that is called hyperpolarization - It is the development of even more negative charge inside the cell ** ALL OF THESE TERMS ARE REFERENCED TO THE -70 MV **

Draw and label figure 6.26a of an electrical synapse. Describe their construction, their properties, and their functional significance. List some body locations where they occur.

- Axon of presynaptic cell - Axon terminal - Gap junction - current flow; conduct electricity from cell to cell (FAST!) - Postsynaptic cell

Using figure 6.40, identify and discuss the brain's limbic system.

- Below the cerebral cortex! - Multiple components, neural networking, lots of connections - Very important in adolescence: we are learning how to survive and leave our parents ... figuring out what promotes our survival? - Structurally: number of connections - Behaviorally: maturity - Sensitive to drugs and alcohol - Olfactory bulbs: physically hardwired to hippocampus... so that is why a scent can trigger a memory - Functions include learning + memory, emotional functions, our appetites, and endocrine integration

Describe neuromodulators; what is their general mechanism of action?

- Default is hydrophilic messenger molecule - Usually small, hydrophilic peptides, co-released with neurotransmitter in vesicle - Activate 2nd messengers at non-synaptic receptors (metabolic receptors) - Can interact with receptors on pre-synaptic or post-synaptic cells to modify effectiveness of the synapse transmitting a signal EX: Anti-histamine

Using figure 6.8, describe how a resting membrane potential (Vm) is measured and what a "typical" Vm is for neurons.

- ECF and ICF have balanced charges: tiny charges of ions along the membrane cause the membrane potential - A typical Vm for neurons is - 70mV

Using figure 6.36, explain the neurophysiology and significance of long-term potentiation.

- Mechanism of learning and memory - Strengthening a synapse - In hippocampus 1. Action potential propagation 2. Release of glutamate (excitatory) from the pre-synaptic terminal 3. AMPA and NMDA are the receptors for glutamate - AMPA is open and will allow depolarization... BUT NMDA is plugged with the Mg2+ ion and won't let ions through - Eventually, the cell will depolarize enough so that the magnesium ion will get pushed out of the pore 4. Now, Ca2+ and acts as a second messenger and can change the strength of the synapse 5. Retrograde messenger *** Alcohol impairs this process ***

Draw and label figure 6.18 to illustrate the conformations of the voltage-gated Na+ channels and voltage-gated K+ channels that underlie the typical neuronal action potential.

- Na+ voltage-gated channels: FAST, RAPID, open and inactivate rapidly; can be open, closed, and inactivated - K+ voltage-gated channels: open and close SLOWLY; much slower than Na+ channels; the "stoners"

Reproduce table 6.3 to ensure your understanding and proper usage of membrane potential terms.

- Potential or potential difference: the voltage difference between two points due to separated electrical charges of opposite sign - Membrane potential: the voltage difference between the inside and outside of a cell - Equilibrium potential: the voltage difference across a membrane that produces a flux of a given ion species that is equal but opposite to the flux due to the concentration gradient of that same ion (a target value) - Resting membrane potential: the steady potential of an unstimulated cell (governed by 1) the pump, 2) potassium leak channels, and 3) sodium leak channels) - -70 mV - Graded potential: THEY COME FIRST... lead to action potentials! ; a potential change of variable amplitude and duration that is conducted decrementally; has no threshold or refractory period - Action potential: a brief all-or-none depolarization of the membrane, which reverses polarity in neurons, has a threshold and refractory period and is conducted without decrement

Describe the interactions between positively and negatively charged particles, and how those interactions are changed depending on the amount of charge and distance of separation. Utilize figure 6.7 for this learning objective.

- Separated charges have the potential to do work (in millivolts) - think of BATTERIES! - Phospholipid bilayer has a high electrical resistance and acts as a capacitor - Open ion channels are a low-resistance pathway for movement of charges, "current", which in Biology is carried by ions / movement of ions is synonymous with the word, "current" - All cells have a potential difference across their plasma membrane (in millivolts) - ECF is assigned 0 mV - "At rest", the membrane potential is negative (inside with respect to the outside) - Exact value varies between cell types - "typical" neuron has a resting value of -70 mV (inside leaflet)

Using figure 6.32a, illustrate the local current flow that underlies an EPSP.

- Slight increase going up

Using figure 6.32b, illustrate the local current flow that underlies an IPSP.

- Small decrease (downhill)

Draw and label figure 6.19. Using the seven talking points, describe an action potential and state how they are different from graded potentials.

- Start at -70 mV - Some graded potentials will summate, and if those graded potentials summate (depolarize enough, we will get an action potential - Threshold = -55 mV - If we hit the threshold, this will open voltage-gated sodium channels - We are heading to +60 mV because that is the Nernst potential (what it wants to be) - BUT... we don't reach +60 because the sodium channels rapidly inactivate (peak) - Then, our slowly-opening potassium channels start to come on board and they want to get to -90 mV - We now have more permeability to K+ and we will go back down to -70 mV - K+ channels will stay open a bit too long, so we will dip right below -70 mV ("after hyperpolarization" - -70 mV to +30 mV in a quick amount of time - Very small numbers of ion cross the membranes

Write the three bullet points that define and describe positive feedback loops.

-An initial change in a particular variable occurs -A response occurs that leads to an increase in the change of this variable -This cycle continues and the response continues to increase

Reproduce table 6.6 and add the talking points from lecture.

1. Acetylcholine - excitatory NT - Nicotine and muscarine receptors help differentiate receptor subtypes - IT IS THE RECEPTORS/ION CHANNEL THAT DETERMINES WHETHER AN IPSP OR AN EPSP DEVELOPS; BUT SOME NT ARE CONSISTENTLY EXCITATORY OR INHIBITORY 2. Biogenic amines - Dopamine - Norepinephrine - Epinephrine - Serotonin - Histamine 3. Amino acids - Excitatory AAs: Glutamate - Inhibitory AAs: GABA and Glycine 4. Neuropeptides - Endogenous opioids (our body makes its own opioids) - Oxytocin: promotes smooth muscle contraction - Substance P: NT involved in transmission of pain 5. Gases - Nitric oxide: relaxes smooth muscle, vasodilation 6. Purines - Adenosine and ATP

Identify 4 types of neuronal glial cells, where they are found, and what function(s) they perform.

1. Astrocytes (looks like gum) - 1) manipulate, regulate, maintain ECF conditions and 2) they seem to reach out and put "hands" on a capillary - this is important for the formation of the blood-brain barrier - Brain neurons are highly protective of what is in the blood! 2. Ependymal cells - 1) line fluid-filled cavities and 2) the produce cerebrospinal fluid 3. Microglia - act as scavengers; very good at removing debris/old things 4. Oligodendrocyte - produce myelin - Myelin sheath is associated with axons of many neurons; made by Schwann cells in PNS and by oligodendrocytes in CNS - 1 Schwann cells makes 1 myelin wrapping - 1 oligodendrocyte can reach out and make up to 40 myelin wrappings!

List the three types of events that regulate the gating of ion channels.

1. Chemical 2. Electrical 3. Mechanical

Compare/contrast the major characteristics of pathways by which substances cross membranes (i.e. the characteristics shown in Table 4.2 and exemplified in figure 4.15).

1. Ion channels (their own category) 2. Primary active transport (use ATP directly) 3. Secondary active transport (Use ion gradients directly) 4. Facilitated diffusion

Use figure 6.23 to explain why action potentials normally propagate in only one direction along axons.

1. It starts at the axon hillock because this is the place where there is the highest density of voltage-gated Na+ channels (positive feedback) 2. Action potentials normally propagate in only one direction because what it leaves behind is the absolute refractory period and it can only go one way, it can't back up. After enough time passes, the earlier patches that DID have the action potential, they are now ready to participate again

List the major properties that determine the function of an ion channel.

1. Membranes are electrically charged 2. Charge on a membrane ion ALSO influences the net flux of charged ions (NOT just the change in concentration) "Electrochemical gradient"

Explain why postsynaptic potentials are brief using four talking points.

1. Neurotransmitter rapidly binds and unbinds 2. Neurotransmitter reuptake into presynaptic terminal and/or 3. Neurotransmitter diffusion away from the synapse and/or 4. Enzymatic deconstruction of neurotransmitter (and reuptake of products)

List two factors that influence the propagation velocity of action potentials along neurons.

1. One-way (starts at axon hillock with refractory period - WHY? Because highest density of voltage-gated sodium channels 2. Myelination increases velocity propagation - Saltatory conduction 3. Velocity increases with axon diameter

Name the two subdivisions of the autonomic motor system, and describe the general effects each has on the body when it is dominant.

1. Parasympathetic - "Rest and Digest" - Homer Simpson 2. Sympathetic - "Fight or Flight" - Fright, flight, fight, and reproduction

Use figure 7.1 to describe two types of sensory receptors.

1. Receptor membrane proteins - Integral membrane proteins on peripheral terminals 2. Receptor cell - Entire cell has integral membrane proteins

Build table 1.2 and discuss the five important generalizations about homeostatic control systems.

1. Stability is achieved by balancing inputs and outputs with each other. 2. A negative feedback loop results in a response that moves a variable in the opposite way that a change caused the set point to move from (it wants to go back toward the "set point") 3. Homeostasis is a dynamic process, it is not static. There is a range of values, not ONE, single one. 4. Set points can change. 5. There is a hierarchy of importance in homeostasis. Some systems have a higher priority than others. Some variables may be changes in order to keep others within normal ranges.

List four properties that distinguish action potentials.

1. They are "all-or-none" (like a gun: either fired or not fired... no inbetween) 2. Are not graded by stimulus size (ECF conditions influence appearance/characteristics) 3. Can NOT summate due to refractory period (absolute/relative refractory periods) 4. Do NOT decrease with distance; they PROPAGATE over long distances because they are large local currents

As in figure 6.34, describe eight ways that synaptic transmission can be altered by drugs and diseases.

A drug might... 1. Increase leakage of NT from vesicle to cytoplasm, exposing it to enzyme breakdown 2. Increase transmitter release into the cleft 3. Block transmitter release 4. Inhibit transmitter synthesis 5. Block transmitter reuptake 6. Block the cleft or intracellular enzymes that metabolize the transmitter 7. Bind to receptor on the postsynaptic membrane to block (antagonist) or mimic (agonist) transmitter action 8. Inhibit or stimulate second-messenger activity within the postsynaptic cell

Define the term "nerve". As in figure 6.42, list the five regions of the spinal cord from top to bottom, state how many spinal nerves are associated with each, and explain what information is carried by spinal nerves.

A nerve is a bundle of axon, and it can be afferent or efferent The five regions of the spinal cord are: - Cervical (8): neck, arms, hands, shoulder, to 1st rib - Thoracic (12): chest, upper abdomen - Lumbar (5): lower abdomen, hips, legs - Sacral (5): lower GI, genitals - Coccyx (1): tailbone

Define the absolute and relative refractory periods. Then sketch figure 6.22 to describe an experiment you could use to determine those periods.

Absolute refractory period: it does NOT matter the strength of the stimulus, YOU WILL GET NO RESPONSE; NOT GET ANOTHER ACTION POTENTIAL Relative refractory period: if we wait a bit of time, and give another stimulus that is STRONGER than the original stimulus, you will get an action potential - Here, if the Na+ conditions > K+ conditions, then we will have an action potential

Using figure 6.4, discuss the locations and general functions of afferent neurons, efferent neurons, and interneurons. Table 6.1 will help you with this objective.

Afferent (sensory) neurons: looks like a little different than general scheme; sensation is detected and we generate a signal in the peripheral terminals; peripheral terminals then gather together and where they converge into a single process is what we call the sensory afferent axon; this sensory afferent axon carries the signal; axon has two parts: - Central process: what actually projects into the CNS - Peripheral process: other side of cell body - Cell body is off to the side in the cul-de-sac - PNS afferent neurons (their activity "affects" what will happen next) into the CNS Efferent neurons: model general scheme of neurons; PNS efferent neurons ("effecting" change: movement, secretion, etc.) projecting out of the CNS Interneurons: model general scheme of neurons; all parts of interneurons are in the CNS

Using figure 3.32, describe and depict both allosteric modulation and covalent modulation of receptors. What changes in both types of regulation? How does the change occur?

Allosteric modulation: receptor is not interested in ligand and doesn't really have a shape fit or charge attraction. Receptor protein has a friend (purple ball), the modulation molecule. Purple ball associates to receptor at another spot, and this changes the shape of the receptor protein and moves the charge over to the right place. Now, protein has affinity for ligand. Modulator molecule leaves after a bit, and then this reverts the protein back to its original shape and the ligand and protein don't have high affinity anymore. This is a noncovalent change (not permanent). In addition, modulator molecules can inhibit association between the ligand and protein (this example just didn't show that). Covalent modulation: receptor is not interested in ligand and doesn't really have a shape fit or charge attraction. An amino acid on the receptor protein is an OH (hydroxyl group), and when amino acids have an OH groups hanging out, they are great targets for enzymes. Kinases phosphorylate proteins (the kinase takes the last phosphate group of ATP and transfer it to OH groups). This is called phosphorylation. This drives the receptor to change shape and have high affinity. This is covalent modulation because you transferred electrons and made bonds. This is an enzyme driven process, so you will need an enzyme to undo it (phosphatase). TASES TAKE.

Using potassium and sodium ions as examples, explain the concept of an equilibrium potential. Write the Nernst equation and discuss what it tells you.

An equilibrium potential results in equal and opposite movements; it's a hypothetical number; it's a target value Nernst Equation: Eion = (61/z) * log (extracellular ion conc. / intracellular ion conc.)

Using figure 4.20, draw and describe the processes of endocytosis and exocytosis.

BOTH processes require ATP, many membrane proteins, and vesicles; bulk movement of macroscopic particles or large proteins into and out of cells ENDOcytosis: movement into the cell; plasma membrane bilayer is going to pinch off; when the bilayer pinches off, it is going to form a membrane-bound vesicle inside the cell with whatever was encapsulated in the ECF EXOcytosis: movement out of the cell (exit); inside the cell, you're going to create a vesicle (with involvement from Golgi organelle); Golgi pinches off these membrane-bound vesicles inside the cell; whatever is inside these vesicles will exit the cell via FUSION - Exocytosis of neurotransmitters

Using figure 4.18, describe what will occur when there are different concentrations of non-penetrating solutes on two sides of a membrane that is permeable to water.

Begin: the partition between the compartments is permeable to water and to the solute. Right now, we have an equal amount of solute and water on each side of the partition (different Osm and M on each side) After diffusion equilibrium has developed: movement of water and solutes has equalized solute and water concentrations of both sides of the partition (same Osm and M on each side) NO VOLUME CHANGE!

Using figure 4.18, explain what osmotic pressure represents and why it is proportional to the amount of non-penetrating solutes.

Begin: the partition between the compartments is permeable to water only (the solute is non-penetrating) and different Osm and M on each side After diffusion equilibrium has developed: movement of water ONLY has equalized solute concentration (so, same Osm and M on each side, BUT there is a VOLUME CHANGE!!!) Osmotic pressure is proportional to the solute concentration; it is the pressure that would have to be applied to stop water from moving into a compartment

Using both words and sketches, define "binding affinity" and clearly distinguish between high, intermediate, and low binding affinity sites.

Binding affinity: likelihood of being associated High affinity: strong association, shape fit, charge attraction ( - and + charges ) Intermediate affinity: moderate association, just shape fit, no charge attraction (or vice versa) Low affinity: weak association, little to no shape fit, no charge attraction

Using figure 6.37, identify and discuss both the functional and the anatomical divisions of the nervous system.

CNS: Brain and spinal cord - The spinal cord integrates, processes, and directs signals (it doesn't just transfer signals)! PNS: Everything else - Afferent division --- Somatic sensory (touch, temperature) --- Visceral sensory (internal organs) --- Special sensory (vision, taste, smell) -Efferent division (away, exit) --- Somatic motor (neurons that influence skeletal movements; usually conscious) --- Autonomic motor (unconscious) ------ Sympathetic (fight or flight) ------ Parasympathetic (rest and digest) ------ Enteric (Gut wall NS) - "trust your gut"

Use Table 1.1 and list the body's organ systems. For each system include the major organs or tissues and the primary function(s) of the system.

Circulatory: Heart, blood vessels, blood; blood transport Digestive: Mouth, salivary glands, pharynx, esophagus, stomach, small and large intestines, anus, pancreas, liver, gallbladder; digestion and absorption of nutrients and water, elimination of waste Endocrine: All glands and organs that secrete hormones - pancreas, testes, ovaries, hypothalamus, kidneys, pituitary, thyroid, parathyroids, adrenals, stomach, small intestine, liver, adipose tissue, heart, and pineal gland - as well as endocrine cells in other organs; regulation and coordination of many activities in the body including growth, metabolism, reproduction, blood pressure, water and electrolyte balance, and more Immune: White blood cells and their organs of production; defense against pathogens Integumentary: Skin; protection against injury and dehydration, defense against pathogens, regulation of body temperature Lymphatic: Lymph vessels, lymph nodes; collection of extracellular fluid for return to blood, participation in immune defenses, absorption of fats from digestive system Musculoskeletal: Cartilage, bone, tendons, ligaments, joints, skeletal muscle; support, protection, and movement of the body, production of blood cells Nervous: Brain, spinal cord, peripheral nerves and ganglia, sense organs; regulation and coordination of many activities in the body including most of those regulated by the endocrine system, detection and response to changes in the internal and external environments, states of consciousness, learning, memory Reproductive: Male: production of sperm, transfer of sperm to female Female: production of eggs; provision of a nutritive environment for the developing embryo and fetus; nutrition of the infant Respiratory: Nose, pharynx, larynx, trachea, bronchi, lungs; exchange of CO2 and O2, regulation of hydrogen ion concentration in the body fluids Urinary: Kidney, ureters, bladder, urethra; regulation of plasma composition through controlled excretion of ions, water, and organic wastes

Using figure 6.25, define and illustrate convergence and divergence with regard to neuronal pathways. Explain the functional significance of each neuronal arrangement.

Convergence: multiple neurons are presynaptic to one neuron Divergence: one neuron is presynaptic to multiple neurons

Reproduce figure 3.4 and differentiate between the cytoplasm and cytosol of a cell.

Cytoplasm: EVERYTHING outside the nucleus Cytosol: the fluid portion surrounding cells

Draw a generic neuron and label the dendrites, cell body, axon hillock, axon, and axon terminals.

Dendrites: receive signals and incoming inputs; look like tree branches Cell body/soma: integration occurs Axon hillock: signal production; signal comes about because within the cell body, there is going to be integration; also known as initial segment or trigger zone Axon: carries signal away from neuron/axon hillock; takes outgoing signal to outgoing terminal

Similar to figure 6.41, draw and label a cross-section of the spinal cord. Highlight the functional relationships and flow of neural signaling in afferent and efferent neurons.

Dorsal root: - Afferent information - Axons carrying information INTO CNS - AKA, central process Ventral root: - Efferent - Signals going out of spinal cord

What are a few examples of positive feedback in the human body?

Examples: blood clotting, childbirth

Define feed forward regulation. How is it different than negative feedback control? Describe some examples of when this occurs in the body.

Feed forward regulation: changes in regulated variables are anticipated, prepared for, and recognized before they even occur; limits the amount of change that occurs, it does NOT prevent it Ex: Salivating when you smell food; temperature-sensitive neurons recognizing a decrease in temperature and sending this signal to the brain before there is even a decrease in our body's temperature

Calculate the equilibrium potential of potassium and sodium ions using the Nernst equation.

For sodium ions = +60 mV For potassium ions: -90 mV

Build table 6.7 and identify the general functions of major brain parts.

Forebrain: -Cerebrum (4 lobes) -- Parietal: sensory information arrives and is processed here -- Temporal: hearing -- Occipital: visual information -- Frontal: reasoning and higher-order thinking - DIencephalon - Thalamus: relay station; distributes signals across, into, and out of the brain; divides our attention between different things - Hypothalamus: master control station for homeostasis; neuro and endocrine control of homeostasis; lots of set points here! Brainstem: unconscious life support; respiratory and cardiovascular control Cerebellum: motor control; coordinates movement; posture and balance

Define functional unit as used in human physiology.

Functional unit: multiple, small, similar subunits found in organs that can still perform the function of an organ

Reproduce table 6.4 to ensure your understanding of differences between graded potentials and action potentials.

Graded potentials: the size of a graded potential is proportionate to the intensity of the stimulus; graded potentials rapidly decay with distance; OCCUR BEFORE ACTION POTENTIAL; - Excitatory graded potential: depolarization is called an excitatory graded potential because it makes an action potential more likely Inhibitory graded potential: graded potentials can also be hyperpolarizing (inhibitory) - this makes an action potential less likely Action potentials:

Using figure 6.39, describe gray and white matter and discuss their functions in the brain.

Gray matter: AKA cortex; contains neuronal cell bodies; it is what makes up the different lobes; about 3 mm thick and there are 6 cell layers within the cortex; info coming into the cortex comes in non-pyramidal cells; and information sent out of the cortex is sent out through pyramidal cells White matter: just beneath gray matter; axons!

Define homeostasis with words and draw the conceptual loop we developed in lecture.

Homeostasis: the process of maintaining a stable internal environment; this is not a static process, it is a state of DYNAMIC CONSTANCY

Use figure 1.10 to define and distinguish between four types of chemical messengers.

Hormones: target cells in one or more distant places in the body Neurotransmitters: neuron or effector cell in close proximity to site of neurotransmitter release Paracrine substance: target cells in close proximity to sit of release of paracrine substance Autocrine substance: acts on the same cell that secreted the substance

Draw figure 5.5 and discuss the properties and steps that a hydrophilic signaling molecule typically utilizes. Also define what an ionotropic receptor is.

Hydrophilic signal molecules - Non-penetrating molecules - Receptor will often be on plasma membrane (b/c hydrophilic molecules are unlikely to go through the lipid bilayer) - Typically have a fast effect because they modify existing proteins - After the molecules binds to the receptor, 1 of 2 things could occur: 1. They alter the shape of ion channels (closed to open -> ions cross receptor) - THIS IS AN IONOTROPIC RECEPTOR - chemical gating 2. They initiate second messenger cascades

Draw figure 5.4 and discuss the properties and steps that a hydrophobic signaling molecule typically utilizes.

Hydrophobic signal molecules - Travel through the capillary - Diffuse out of the capillary and the messenger will go through the plasma membrane - The receptor will most likely be in the nucleus of the target cell - When the ligand binds to the receptor, it will alter gene transcription and protein synthesis - They typically have a slow effect because they're inducing the synthesis of new proteins - Also long-lasting because you're creating new proteins EX: Steroid hormones (testosterone, estrogen, progesterone)

State the typical concentrations of Na+ and K+ in the intracellular and extracellular fluid. Explain what is responsible for maintaining the extracellular concentrations and what is responsible for maintaining the intracellular concentrations.

INTRACELLULAR Na+ = 15 mM K+ = 150 mM -The pump in the membrane regulates the intracellular concentrations EXTRACELLULAR Na+ = 145 mM K+ = 5 mM -Extracellular concentrations are maintained by the kidneys

Discuss the main factor that determines the selective permeability of lipid bilayers. Identify and describe substances that are permeable, substances that are not permeable, and explain how substances that are not permeable are in fact able to cross living cell membranes.

It is mainly the hydrophobic core made by the fatty acid tails of the phospholipids, NOT the hydrophilic head group of the phospholipid that determines the selective permeability of the lipid bilayers. Hydrophobic (lipid soluble) and/or very small polar substances are easily permeable Ex: oxygen, carbon dioxide, ethanol, steroid hormones. Hydrophilic substances, including large polar molecules and ions can NOT go across the membrane without transport proteins or ion channels.

State the chemical function of cholesterol in the plasma membrane.

It is the "Goldilocks Lipid" - it is looking for things that are just right. We want the fatty acid tails in the lipid bilayer to stay together; we don't want them to fall apart. Cholesterol helps to keep those fatty acid tails together and from flying apart. However, the tails are supposed to be a fluid environment, and if they are too stuck together, they form a solid. Cholesterol ensures there is a happy medium.

Describe what is meant by a "membrane leaflet". Are the lipid components the same in each?

Membrane leaflet is synonymous with a membrane layer. Therefore, since we have a lipid BI-layer surrounding the plasma membrane, we have two layers (two leaflets). One leaflet (head and tail) faces the EXC and one leaflet faces the ICF (head and tail). No, the two leaflets actually differ. The phospholipids are not the same, they differ in phospholipid composition.

Explain the difference between molarity (moles per liter) and osmolarity (osmoles per liter).

Molarity: the number of moles of solute per one liter of solution Osmolarity: total solute concentration / liter of water - A solution that is 1 mole/liter of NaCl has an osmolarity of 2 osmoles/liter -NaCl dissociates into two ions in water from one molecule

Use figure 1.1 and list the four basic tissue and cell types.

Muscle, connective, epithelial, nervous

Functionally and chemically distinguish between integral and peripheral membrane proteins.

My distinction: how would you get each type of protein out of the membrane? Integral membrane proteins: have a substantial interaction with the fatty acid tails of the lipid bilayer; you must bust up the plasma membrane, add detergents, destroy plasma membrane, amd disrupt interactions with the fatty acid tails; these proteins are extremely structurally attached Peripheral membrane proteins: you change the fluid conditions (change the pH, salt concentration) and that is enough for the protein to dissociate from the membrane

First, using your lecture notes, reproduce our derivation of Ohm's Law that we will use in human physiology. Second, use figure 6.12 to apply Ohm's Law, to apply electrochemical gradients, and to explain how net ion movement across a membrane is determined.

Ohm's Law: V = I * R Voltage = Current * Resistance and in physiology, we replace 1/R with g... I = V * g "g" represents the number of channels available to us and their characteristics; basically, can the ion get across the membrane, yes or no? We also need to consider the DRIVING FORCE ON THE ION and replace V with (Vm - Eion) = enthusiasm of ion to move through a challen Ohm's Law as used in physiology: Iion = gion * (Vm - Eion)

From table 6.8, discuss the functions served by cranial nerves II, IX, X, and XI.

Optic - Afferent - Carries input from receptors in eye Glossopharyngeal - Efferent: innervates skeletal muscles involved in swallowing and parotid salivary gland - Afferent: transmits information from taste buds and receptors in auditory-tube skin; also transmits info. from carotid artery baroreceptors Vagus - Efferent: innervates skeletal muscles of pharynx and larynx and smooth muscle and glands of thorax and abdomen - Afferent: transmits info. from receptors in thorax and abdomen Accessory - Efferent: innervates sternocleidomastoid and trapezius muscles in the neck

Using table 4.3, define and differentiate between solutions described as: isotonic, hypertonic, hypotonic, isosmotic, hypoosmotic, hyperosmotic.

Osmolarity: includes ALL solutes (P + NP) Tonicity: only considers the non-penetrating solutes Isosmotic: a solution containing 300 mOsm/L of solute, regardless of its composition of membrane-penetrating and NP solutes Hyperosmotic: a solution containing greater than 300 mOsm/L of solute, regardless of its composition of membrane-penetrating and NP solutes Hypoosmotic: a solution containing less than 300 mOsm/L of solute, regardless of its composition of membrane-penetrating and NP solutes

Using the information in table 6.9, draw and describe efferent autonomic innervation details.

PARASYMPATHETIC: Soma in CNS, axon extends into PNS and releases acetylcholine to another neuron, this second neuron has a varicosity (SWELLING!) AND releases ACH to muscarinic receptor SYMPATHETIC: 1. Soma in CNS, axon goes out a little and releases acetylcholine, another neuron extends and releases epinephrine/norepinephrine from a varoscocity 2. Soma in CNS, axon goes out a little and releases acetylcholine to a blood vessel, epinephrine/norepinephrine from blood vessel

Draw figure 5.12 and describe the steps of the PLA2-ARA signal transduction cascade.

PL2-ARA SIGNALING CASCADE: -Our starting point is a receptor-ligand complex (still a metabotropic receptor) - This complex will lead to the activation of an enzyme called Phospholipase A2 - BUT... is there a G protein here somewhere? The answer is yes, maybe - The target of Phospholipase A2 is phospholipids, in particular, the A2 is this signature tells us that this enzyme targets the 2nd fatty acid tail (ARACHIDONIC ACID!) - Phospholipase A2 releases arachidonic acid from the membrane - Arachidonic acid is hydrophobic, so when it is released, it could go into or out of the cell 1. If arachidonic acid encounters a cascade of enzymes called cyclooxygenases, it will produce PROSTAGLANDINS - Prostaglandins are important in vascular actions, inflammation, and PAIN 2. If arachidonic acid comes into contact with lipoxygenases, it will create leukotrienes - Leukotrienes are important in allergic reactions and inflammatory reactions

Draw figure 5.10 and describe the steps of the PLC-PKC signal transduction cascade.

PLC-PKC CASCADE: - Metabotropic receptor binds our hydrophilic, first messenger molecule - This activates a G protein (Gq) - most chic protein - Gq activates an enzyme called phospholipase C - Phospholipase C targets phospholipids (chews them up and breaks them down!) - Phospholipase C specifically targets the phospholipid called PIP2 - PIP2 is more likely to be found on the inner leaflet - The headgroup of PIP2 is called IP3 - IP3 is released from the membrane when the phospholipid is chewed up by phospholipase C - IP3 is now a SECOND MESSENGER! It is released into the cell - IP3 finds a receptor (an ion channel) on the ER - if the receptor is an ion channel, which this one is, we call it an IONOTROPIC RECEPTOR! - This receptor allows Calcium to come out of the smooth ER - When released, the Calcium can activated a kinase called protein kinase C (PKC) - The calcium that is released from the smooth ER can also be a second messenger of its own

Explain how the terms negative feedback and positive feedback relate to the function of voltage gated Na+ and K+ channels during a typical neuronal action potential.

POSITIVE FEEDBACK Start: depolarizing stimulus - Opening of voltage-gated Na+ channels - Increased PNa - Increased flow of Na+ into the cell - Depolarization of membrane potential - Repeat... Stop: inactivation of Na+ channels NEGATIVE FEEDBACK Start: depolarization of membrane by Na+ influx -Opening of voltage-gated K+ channels - Increased PK - Increased flow of K+ out of cell - Repolarization of membrane potential - Repeat...

Define and distinguish between Physiology, Anatomy, and Pathophysiology.

Physiology: the study of how living organisms FUNCTION Anatomy: the study of the STRUCTURES of different body parts Pathophysiology: the study of diseases states (dysfunctional physiology)

Using figure 1.3, draw and label a diagram that illustrates the major fluid compartments of the body. With labels for each compartment, indicate the volumes in an average-sized person.

Plasma (ECF): Fluid around blood cells (3 L) Interstitial fluid (ECF): Fluid between cells (11 L) Intracellular fluid: Fluid inside of cells (28 L)

Why are plasma membranes described as Fluid Mosaics?

Plasma membranes are described as "Fluid Mosaics" because there is so many different molecule working together and distributed along the plasma membrane, like a mosaic is made from multiple tiles. These molecules are also constantly in motion in a fluid-like fashion.

Reproduce table 6.5 which summarizes the factors that determine synaptic strength.

Presynaptic factors - Availability of NT - Axon terminal for membrane potential - Axon terminal Ca2+ - Activation of membrane receptors on presynaptic terminal - Certain drugs and diseases Postsynaptic factors - Immediate past history of electrical state of postsynaptic membrane - Effects of other NTs acting on postsynaptic neuron - Up/downregulation and desensitization of receptors - Certain drugs and diseases General factors - Area of synaptic contact - Enzymatic destruction of NT - Geometry of diffusion path - NT reuptake

Using figure 4.11, draw and describe primary active transport. Then describe the molecular details of the Na+/K+-ATPase pump as it is working.

Primary active transport: requires energy input (usually ATP); crucial for cellular life; moves solute against conc. gradient ("active"); primary because the same protein that is moving the solute is also hydrolyzing ATP; has binding sites EX: 3 sodium ions move from inside the cell to the outside of the cell. 2 potassium ions will move from outside the cell into the inside of the cell (this occurs as a phosphate group is released and a new ATP comes on to the transport protein)

Using figure 3.29, define and depict a receptor and a ligand.

Receptor: protein that a ligand binds to Ligand: ANYTHING that binds to a receptor

Using figure 7.17 as an example, define a referred pain and describe the mechanism that causes this phenomena.

Referred pain is due to the fact we have pain receptors all along our body; it is an example of convergence (multiple axons communicate to one)

Using figure 4.13, draw and describe secondary active transport. Then describe what cotransport (aka symport) and counter-transport (aka antiport) indicate. Use figure 4.14 to draw examples of each.

Secondary active transport: protons, glucose, amino acids; movement AGAINST a concentration gradient; does NOT hydrolyze ATP; energy provided by another molecule's concentration gradient' primary active transport comes first and THEN secondary active transport can occur because sodium ion concentration gradient is in place EX: sodium ions will want to move from outside the cell into the inside of the cell (in the direction of the concentration gradient). Sodium gradient is big, there is lots of energy. A low solute concentration on the outside of the cell will utilize this big energy from the sodium ion gradient to move AGAINST the solute gradient into the cell as well. COTRANSPORT: the ion and the second solute cross the membrane in the same direction COUNTERTRANSPORT: the ion and the second solute move in opposite directions

Use figure 5.8 to discuss the amplification principle of signaling cascades.

Signal amplification is a key feature of signaling cascades - 1 receptor with 1 ligand bound to it can give you 100 cAMP molecules (100 second messengers) - Ultimately, it can lead to 1,000,000 phosphorylated products

Using a combination of figures 4.1, 4.2 and 4.3, define and differentiate between simple diffusion, net diffusion, and an equilibrium state.

Simple diffusion: random movement and has no direction; initially higher concentration of molecules randomly moves toward lower concentration Net diffusion: when we see a direction, a net movement, a net directional change; high concentration to low concentration; once we get to equilibrium, there is no net diffusion, only simple diffusion is occuring; accounts for solute movement in both directions and tells you the net direction Equilibrium state: equal flux in both directions

Use figure 1.1 and list the four levels of organization in the human body, from smallest to largest.

Smallest: Cells Tissues Organs Largest: Organ systems

Using the information in table 6.9, draw and describe in detail the somatic efferent neurons.

Soma in CNS, long axon, releases acetylcholine to skeletal muscles

What types of efferent neurons comprise the efferent division of the PNS? List the effectors of each type.

Somatic motor: to skeletal muscles - Single neuron between CNS and skeletal muscles - Innervates skeletal muscles - Can only lead to muscle excitation Autonomic motor: to smooth muscle, GI tract, heart; glands; usually not conscious control - Two neuron chain connected by synapse between CNS and effector organs

Use figure 1.9 to discuss the mechanisms of body core temperature regulation via negative feedback.

Stimulus (decreased body temp.) Temperature-sensitive neurons work as receptors and recognize the stimulus. They increase their signaling rate through an afferent pathway. The integrating center (specific neurons in the brain) compare this change to a set point and alter rates of firing. A signal is sent through an efferent pathways (through nerves) to either the smooth muscle (effectors) in skin blood vessels (so that they will contract) or to the skeletal muscle (also an effector) so that they will also contract, resulting in shivering Decreasing blood flow (response) decreases heat loss. Shivering increases heat production (response). A negative feedback loop occurs.

Use figure 6.21 to illustrate and define subthreshold, threshold, and suprathreshold stimuli.

Subthreshold: do NOT get us to the threshold value; no action potentials Threshold stimulus: gets you to -55 mV; action potential occurs; these stimuli could be sensations or neurotransmitters Suprathreshold: any stimulus that is stronger than threshold

Using figure 6.5, draw and define a synapse, a presynaptic neuron, a neurotransmitter, and a postsynaptic neuron.

Synapse: gaps; neurons communicate at chemical synapses; neurotransmitters will be released by one neuron -> will diffuse through synapse -> go to next neuron Presynaptic neuron: TOWARDS the synapse; neurotransmitters chemicals are released by presynaptic neurons and act on postsynaptic neurons Neurotransmitter: chemical messenger Postsynaptic neuron: AWAY from synapse; neurotransmitters chemicals are released by presynaptic neurons and act on postsynaptic neurons - Neurons can be both pre and postsynaptic depending on directionality

Using figure 6.31, explain synaptic integration and define both temporal and spatial summation.

Synaptic integration allows for fantastic complexity: - Postsynaptic potentials are graded - Individual PSPs are small in neurons (0.5 mV) - Summation of PSP's allows neuron integration at initial segment Temporal summation: 1 INPUT ONLY Spatial summation: 2 OR MORE PRESYNAPTIC INPUTS BEING SUMMATED

Explain why intracellular fluid and extracellular fluid Na+ and K+ concentrations are different, and state the typical values found in each compartment (utilize Table 6.2).

The concentration differences for Na+ and K+ are established by the action of the Na+/K+ ATPase pump that pumps out 3 Na+ ions and lets in 2 K+ ions. ICF: - Na+ = 15 - K+ = 150 ECF: - Na+ = 145 - K+ = 5

Using figure 4.16, explain the principle of osmosis.

The concept of osmosis: the diffusion of water toward more solutes

Using figure 1.4 and blood glucose levels, explain the essence of homeostasis.

The essence of homeostasis is that it does not imply that a given physiological function or variable is rigidly constant with respect to time but that it fluctuates within a predictable and often narrow range. When disrupted above or below the normal range, it returns to normal.

State the main role of the nervous system in maintaining homeostasis.

The nervous system is a control system that receives information about the internal (ECF) and external environment, integrates it, and directs activities of cells throughout the body to maintain homeostasis - 1 of 2 control systems

Use figure 1.8 to show how the five components of a negative feedback system sense and respond to a deviation from normal.

The reflex arc: a stimulus occurs, this stimulus is detected by a receptor, the stimulus acts on the receptor to produce a signal relayed to the integrating center along the afferent pathway, the integrating center sends out an output signal to the effector along the efferent pathway resulting in a response

Write the equation that applies Fick's Law of diffusion to biological membranes.

These factors influence the rate of diffusion (J) across a membrane: - Permeability of the substance (P) - Molecular surface area (A) - Molecular weight/size of diffusing substance (MW) - Concentration gradient across the membrane (deltaC) - Distance over which the substance must move (deltaX) Fick's Law: J = (P * A * deltaC * temperature) / (MW * deltaX)

Using figure 6.13, summarize in 3 steps how a resting membrane develops, beginning from a state where there is no membrane potential.

This of the resting membrane potential (RMP) as a step-wise process, beginning from a state where there is no membrane potential: 1. Turn pump on; pumps sets up the Na+/K+ concentration gradient and this sets the Eions 2. Open up a large "leak" permeability for potassium; at first, more K+ diffuses (closer to -90) -BUT... you don't get to -90 because there is a small Na+ leak. Not bigger than K+ leak, but enough to prevent you from getting to -90. -Not at Ena or Ek 3. Na+ and K+ then both move at the resting steady state (-70), not an equilibrium because ATP is required to keep fluxes equal - -70 mV is going to be a constant value for us unless something happens, but it is NOT an eq. value because you require ATP use

Explain and differentiate action potential propagation in unmyelinated versus myelinated neurons. Use figure 6.24 to define and illustrate "salutatory conduction".

Unmyelinated neurons: - Time is required for each patch to depolarize - Propagation over large distances possible - Size of patch is dependent on a particular axon and quite variable in size - Na+ channels ALL ALONG AXON Myelinated neurons: - There are no Na+ channels under myelin - Na+ channels are clumped in the nodes of Ranvier - So, the APs occur at the nodes (So, APs can "jump" along the axon from node to node) - Saltatory conduction: action potentials jump from one node to another as they propagate along a myelinated axon (MUCH FASTER!) - Myelination increases velocity propagation

Using figure 6.9, reproduce the talking points that summarize our starting point of the membrane potential concept.

Usual starting point: ECF and ICF have balanced charges (both are electroneutral); tiny numbers of ions along the membrane cause the membrane potential - Membrane potential changes ONLY when a current flows across the membrane; the major ions involved are Na+, K+, Cl- (and in some cells, Ca2+) - Only a very thin shell of charge difference is needed to establish a membrane potential (very few ions flux to get substantial potentials) - No ion flux or flow, No vM!!!!! (No membrane potential) - The Na+/K+ ATPase pump creates and maintains ion gradients while the kidneys maintain ECF concentrations

Define and discuss resistance, voltage, capacitance, and current as they apply in biological systems.

Voltage: the charge of the membrane potential (could be negative or positive or 0) Capacitance: a cell's capacitance determines how quickly the membrane potential can respond to a change in current Current: movement of charges due to ions moving

Explain the difference in relationship between Vm and ECl- for cells with chloride pumps and cells without chloride pumps.

WHAT HAPPENS WHEN YOU OPEN UP CHLORIDE CHANNELS? - Type 1 cells: K+ and Na+ set the Vm, [Cl-] gradient follows (Ecl- = Vm) - NO CHLORIDE PUMP! - In Type 1 neuronal cells, the RMP IS THE SAME AS THE EQUILIBRIUM POTENTIAL FOR CHLORIDE - In type 1 cells, the target value is 70 mV and the RMP is -70 mV - So, when the Cl- channel opens, nothing will happen bc you're already at equilibrium (no enthusiasm) - Type 2 cells: Minor Cl- pumping (Ecl- < Vm) - CHLORIDE PUMP! - Cl- pump can take it from 7mM and lower the Cl- concentration even more than in Type 1 cells -> leading to an even bigger Cl- concentration gradient -> which will require an even bigger electrical gradient to oppose it - Vm = - 70 mV - Ecl- = -79 mV - If you open a Cl- channel, you will observe change!! Not a huge difference, BUT there is still enthusiasm

Given that lipid bilayers are not very permeable to water, explain how water is able to permeate cell membranes in physiologically relevant amounts.

Yes, water is polar, BUT it is small enough to go across membranes. However, the amount of water that can cross on its own through the membrane is NOT a sufficient amount for out physiology. Water can cross most cell membranes due to water channels called AQUAPORINS. They are protein channels that allow water to cross the membrane in reliable and quantitative amounts.