Membrane Physiology 2/3-2/5

Question 1

What is the ionic composition of the ICF vs. ECF?

Answer 1

ICF– low Na+ (14 mM), high K+ (100mM), variable Cl- (3-30 mM), low Ca2+ (10^-7 mM);
ECF– high Na+ (140mM), low K+ (3.5-5 mM), high Cl- (100 mM), higher Ca2+ (10^-3 mM)

Question 2

What is the role of cell membranes in maintenance of body fluid composition?

Answer 2

cell membrane is a barrier that separates intracellular and extracellular fluid compartments; it is a lipid bilayer that is impermeable to ions due to repulsion of charge by the nonpolar membrane; membrane transport proteins facilitate the shuttling of ions across membranes

Question 3

What is Solubility-Diffusion permeability?

Answer 3

a measure of how easy it is for ions to enter the bilayer (partition coefficient, B) and move through the bilayer (diffusion coefficient, D) with respect to membrane thickness (delta X);
P = BD/delta (x)

Question 4

What are the types of ion transport mechanisms?

Answer 4

Facilitated diffusion (Leaks): ion channels and carriers
Active transport (pumps): primary or secondary (coupled)

Question 5

Describe leak transport

Answer 5

Leaks are processes that are naturally driven to and equilibrium state; that is movement of ions down their concentration gradient. Ion channels and carrier proteins are two leak pathways.

Ion channels are conduction pores that allow rapid permeation of ions; open/closed states; classified by ionic selectivity and sensitivity to blockers/agonists. No conformational change in ion channels.

Carrier proteins undergo a conformational change to facilitate to binding, passage, and release of a molecule across membranes; are slower than ion channels. I.e. glucose transporters (GLUT1-GLUT5).

Question 6

Describe pump transport

Answer 6

An active transport system that uses energy to move a molecule/ion up its concentration gradient; away from equilibrium. Two types of Pumps: 1’ and 2’:

Primary transporters: directly use energy of ATP to move molecule up its conc. gradient; ex. ATPases

Secondary transporters: use energy stored in concentration gradient to transport another ion/molecule. Two types: co and counter transport.

Co-transport: aka symporters; move two molecules/ions in same direction using the energy from the conc. of one.

Counter transport: aka antiporters; moves two ions/molecules in opposite direction.

Question 7

Explain how pump and leak systems modulate the “steady-state” of the cell.

Answer 7

The steady state is the NON-EQUILIBRIUM state that can only be maintained by expenditure of energy by the pump. Leak and pump systems are operating simultaneously and when they are transporting at the same rate, there is no net change in ion concentration in the cell. If the pump system were inhibited, the leak system would continue to transport ions until it reached its equilibrium; after which no flux would occur.

Question 8

Describe the driving forces of passive flow and how we can determine the direction and magnitude of the force.

Answer 8

Compare the work per mole for the concentration gradient with that of the electrical gradient. The larger force will determine the direction of passive flow, and the difference will determine the strength of the force.

Conc. gradient = RT*ln(C1/C2), 
where R (gas constant) = 8.3 Joules/mole-K', and T (absolute temp in Kelvins, K)= T (in celcius) + 273; at room temp, RT=2.57 J/mol

Electrical gradient = zF(delta V),
where z is the valence (equiv/mole), F (faraday’s constant) = 96,500 coul/equiv, and delta V is the membrane potential (-60 mV intracellularly).

Convert work measured in Joules/mole to volts by dividing by zF.

Question 9

What is the electrochemical gradient?

Answer 9

Refers to the electrical potential and chemical concentration difference across the membrane, written as “delta u” which expresses magnitude and direction.
When delta-u= 0, driving force for passive flow is zero, system at equilibrium

When delta-u is > or < 0, there is a driving force.

Question 10

How can you identify active transport?

Answer 10

If the transmembrane solute distribution lies away from equilibrium, then there must be active transport.

Question 11

How are ion channels classified?

Answer 11

By their ion selectivity (Na+, K+, Ca2+, Cl-) and their sensitivity to blockers and agonists (ACh, Glutamate, etc.)

Question 12

Describe the structure of K+ channels

Answer 12

tetrameric proteins with a pore domain and sensor domain. The sensor domain open/closes channel in response to change in memb. potential or ligand binding. The pore (which provides pathway for ions to travel) contains a selectivity filter which is a series of ion binding sites that are specific for K+ (not favorable for Na+), thus allowing the ion channel to be selective/transport one type of ion.

Question 13

what is single channel conductance?

Answer 13

process by which and ion leaves an aqeous solution and enters a channel, translocates thru the channel, and exits on the other side of the membrane.

Question 14

Define depolarization, repolarization, hyperpolarization, and overshoot as related to membrane potential.

Answer 14

Depolarization = membrane potential becomes less negative
Repolarization = membrane potential moves twds resting potential
Hyperpolarization = membrane potential becomes more negative
Overshoot= membrane potential becomes positive inside the cell.

Question 15

Describe voltage-gating and inactivation processes

Answer 15

Voltage gating: channel is closed at resting membrane potential. A depolarization will cause conformational change in channel protein thus opening the channel.

Inactivation: channel opens upon depolarization, like in voltage-gating, but if the membrane remains depolarized, the pore of the channel will be occluded by the N-terminal of channel protein, thus inactivating the channel. Referred to as “Ball and Chain” mechanism

Question 16

What is the origin of membrane potential?

Answer 16

Must have a gradient of ions across a membrane and must have a membrane that is semipermeable (only permeable to 1 type of ion) in order to generate a membrane potential. Ion channels (leaks) are more important to generation of membrane potential than are pumps.

Question 17

Explain how reduction in chloride conductance in the skeletal muscle membrane, such as in congential myotonia, renders the Vm less stable and more likely to fire AP?

Answer 17

Chloride conductance is relatively high and distributed at resting membrane potential, that is Vm = Ecl. So Vm is “clamped” at its resting value under normal chloride conductance conditions. When you remove Chloride conduction, the Vm becomes destabilized, and sodium conductance can more easily depolarize the membrane toward an AP. Ex. “fainting goats” have Cl channel mutation so membrane potential is more hyperexcitable. When goats get startled they fire AP immediately, but cannot repolarize quickly, so they collapse.

Question 18

What is meant by an AP as a “self-reinforcing signal”?

Answer 18

AP propagate over long distances, but retain their same shape and size. All AP’s are a constant shape/size, but the frequency at which a AP is fired corresponds to a variation in what the signal is.

Question 19

How do an AP alter the ion concentration gradient across the membrane?

Answer 19

During an AP very few ions actually cross the membrane, so relative conc. of K+ and Na+ ions on either side of the membrane remains mostly unchanged. The small # of ions that do move during an AP are quickly restored to their normal ion conc. gradient by Na/K ATPase pumps.

Question 20

Explain the relationship between axon diameter and conduction velocity.

Answer 20

Increasing axon diameter increase conduction velocity.

As the axon diameter increases, both the axoplasmic resistance (Ra) and the resistance of the axon membrane (Rm) will decrease, with Ra decreasing faster than Rm. So The higher the Rm and the lower the Ra corresponds to faster conduction velocity. So the larger the axon diameter, the larger Rm/Ra –> faster conduction rate.

Question 21

How does myelination affect conduction rates?

Answer 21

Myelin sheaths around axons creates a high resistance barrier that prevents flow of ions out of the cytoplasm, therefore myelination increases Rm and thus increases conduction rates.

Question 22

What is osmotic pressure?

Answer 22

It is the pressure that must be applied to a solution to stop the influx of water from an equal volume of pure water.
Osmotic pressure is determined by # of particles in a solution and does not depend on size/chemical nature of the particles.

Question 23

What is the difference between molality and molarity?

Answer 23

MolaLity is the # of moles of solute per Liter of Solution (mol/L).

MolaRity is the # of moles of solute per Kilogram of Solution (mol/Kg).

Question 24

What are metabotropic receptors? How do they compare to ionotropic receptors?

Answer 24

Receptors for NTs can be classified as metabotropic or ionotropic depending on how the receptor and effector system are coupled.

Metabotropic: G-protein-coupled receptors (GPCR) gate channels/activate other substrates indirectly by activating G-proteins that engage an effector (2’ messenger) enzyme. Fxn more slowly than ionotropic receptors and also amplify signal from NT. Consists of a single subunit of 7 domains.

Ionotropic: bound NT to a receptor directly opens ion channel. A much faster mechanism than metabotropic receptors. Does not amplify signal. Consists of many subunits.

Question 25

What are the 2’ messenger systems to which G-proteins are coupled to?

Answer 25

activation of adenylate cyclase (cAMP cascade), activation of phospholipase C (DAG-PIP) or phospholipase A (arachidonic acid) pathways.

Question 26

What are the various actions of secondary messengers on ion channel fxn?

Answer 26

1. Amplification of Signal: 2’ messengers can inactivate an ion channel leading to membrane depolarization (cAMP activates PKA –>–> closure of K+ channels—>membrane depolarization). But 2’ messengers can also lead to membrane hyperpolarization and thus inhibition of synaptic transmission.
2. Sec. messengers, once activated, can diffuse to distant parts of the cell.
3. Have slower time course: ex. LHRH a NT that induces very late/slow EPSP’s–time course of 10 minutes.
4. Have longer lasting effects. Ex. when K+ channels are closed at resting membrane potential, can lead to longer lasting depolarization.

Question 27

What is receptor desensitization?

Answer 27

The progressive inactivation of the receptor due to the continuous presence of the NT.

Question 28

What is homologous desensitization?

Answer 28

The process in which a receptor that is targeted by a NT downgrades its activity overtime, despite continued stimulus from an NT.

Example: Beta-adrenergic receptor, which is activated by binding from agonist, undergoes rapid desensitization. This is due to the phosphorylation of the receptor by GPCR kinases, which leads to binding of the receptor to an arrestin protein which creates steric hinderance blocking receptor-NT binding. These modified receptors can be sequestered away from the membrane and either degraded or recycled back.

Question 29

What is heterologous desensitization?

Answer 29

The response of a receptor to an NT is attenuated by activation of another receptor which may share a common or distinct signaling pathway.

Example: M2-muscarinic receptor (which activates K+ channels) can be desensitized by activation of M3-muscarinic receptors, which stimulate phospholipase C, which hydrolyses PIP2, destabilizing/inactivating K+ channels.