Lecture 3: Voltage-Dependent Membrane Permeability

Question 1

Describe the voltage clamp method

Answer 1

1. one internal electrode (connected to the voltage clamp amplifier) measures membrane potential
2. the voltage clamp amplifier compares membrane potential with the desired (command) potential
3. when the membrane potential is different from the desired potential, the clamp amplifier injects current through a second electrode, this feedback arrangement causes the membrane potential to become the same as the command potential
4. the current flowing back into the axon and thus across its membrane can be measured, permitting the measurement of the exact current needed to keep the cell at a given voltage

Question 2

What happens when membrane potential and command potential are the same?

Answer 2

The feedback causes the membrane potential to remain constant

Question 3

What happens to membrane current when you apply and hold a hyperpolarizing current?

Answer 3

get a capacitive current, caused by redistribution of charge across the neuronal membrane and occurs briefly but holding the current doesn’t do anything to the membrane current

Question 4

What happens to membrane current when you apply and hold a depolarizing current?

Answer 4

get a capacitive current then a transient inward current that goes back to 0 and if you hold the current, get a delayed outward current after a few seconds

Question 5

What is axon membrane permeability dependent on?

Answer 5

voltage

Question 6

What happens to membrane current at several different depolarization potentials?

Answer 6

from negative, zero, and increasingly positive mV: small transient inward curve and delayed outward curve, then larger transient inward curve and delayed outward curve, then smaller transient inward curve but a larger delayed outward curve, then transient inward curve lost but a larger delayed outward curve and then transient inward curve slightly outward and larger delayed outward curve

Question 7

What ion is responsible for the transient inward curve?

Answer 7

sodium

Question 8

What happened when sodium was removed from the extracellular saline solution?

Answer 8

The early inward curve is gone, now a small early outward current and a big outward curve

Question 9

Describe the pharmacological separation of sodium and potassium currents into sodium and potassium components

Answer 9

When they added tetrodotoxin, it blocked Na+ channels, and the transient inward curve was gone but the delayed outward curve was there
When they added tetraethylammonium (TEA), blocked K+ channels and when they held the MP to 0, still got transient inward current but the delayed outward current was gone so the delayed outward current is dependent on potassium

Question 9

What did the experiments regarding the membrane changing to a more positive level than resting potential produce?

Answer 9

An early influx of Na+ into the neuron produces a transient inward current.
A delayed efflux of K+ produces a sustained outward current.

Question 10

In general, what effect does depolarization have on sodium and potassium conductance?

Answer 10

Increases

Question 11

What does depolarization of the neuronal membrane result in?

Answer 11

(1) Na+ conductance activation
(2) K+ conductance activation
(3) Na+ conductance inactivation

Question 12

true or false: sodium and potassium conductances change over time

Answer 12

true

Question 13

true or false: sodium and potassium conductances are voltage-dependent

Answer 13

true

Question 14

What happens if you stimulate the membrane potential at a time close to the first action potential?

Answer 14

nothing happens because of the refractory period (Na+ channels are inactivated) but if you wait a bit longer, you can generate an AP but now you’re stimulating a membrane that’s been hyperpolarized, resulting in a smaller amplitude AP

Question 15

What feedback cycles are responsible for membrane potential changes during an action potential?

Answer 15

the fast positive cycle and slow negative cycle

Question 16

What happens in the fast positive and slow negative cycles?

Answer 16

when you depolarize this leads to Na+ channels opening, leading to an increase in Na+ current which further depolarizes the current but eventually Na+ channels become inactive and while this happens, it has a slower effect that opens K+ channels and this hyperpolarizes the membrane potential

Question 17

true or false: action potential conduction doesn’t require both active and passive current flow

Answer 17

false, it requires both

Question 18

Explain the steps of action potential conduction

Answer 18

1. A certain point on the axon is stimulated, resulting in an action potential due to local sodium channels opening
2. passive current flow moves down the axon and decays but it can lead to local depolarization at a new point on the axon which causes sodium channels to open at this new point and generates an action potential
3. upstream sodium channels get inactivated while some potassium channels open and now the membrane is repolarizing at the previous point and it’s in the refractory period
4. this process repeats continuously, due to a delay as passive current is activating point B after point A and activating point C after point B

Question 19

What is the role of the refractory period?

Answer 19

Limits the number of APs that a neuron can produce per unit time
Prevents re-excitation of the same membrane segment that was just excited
Prevents APs from propagating backward toward their point of initiation

Question 20

What is conduction velocity?

Answer 20

how long it takes for an AP to propagate from one end of a neuron to the other

Question 21

What are the 2 ways to increase conduction velocity or passive flow?

Answer 21

Increase the axon diameter
Myelinate, which leads to saltatory conduction in which generation of the AP occurs only at the Nodes of Ranvier, which is the only place along the axon where voltage-gated Na+ channels are found

Question 22

Where are sodium channels found in myelinated neurons?

Answer 22

Nodes of Ranvier

Question 23

true or false: Nodes of Ranvier are myelinated

Answer 23

false

Question 24

What is the advantage of myelination?

Answer 24

Allows passive flow of current further down the axon, faster vs. an unmyelinated axon

Question 25

What is multiple sclerosis?

Answer 25

a disease of the central nervous system that is characterized by a variety of clinical problems that arise from demyelination and inflammation of axonal pathways

Question 26

What is thought to be the cause of multiple sclerosis?

Answer 26

the immune system produces antibodies against myelin proteins, leading to demyelination, and disrupts an axon’s ability to conduct APs, which is why you see a variety of clinical problems