Action Potential Generation

Question 1

At what membrane potential does the Na activation gates open

Answer 1

-50 V, which is the threshold potential

Question 2

Is threshold a fixed value

Answer 2

It is not a fixed value even though some textbooks emphasize the fact that it is fixed. It changes as it depends on the number of voltage gated Na channels and the number of K repolarizing channels.

In another slide he said it depends on the balance of the depolarizing current and repolarizing current

Question 3

Explain the initial steps of depolarizing current in terms of electrophysiology once the threshold potential is reached

Answer 3

1. Both of the gates, the activation gate and inactivation gate for Na channels open
2. Conductance of Na increases (gNa as well as fNa)
3. Na ions as a result flow into the cell, this is depolarizing current, flow of current into the cell
4. Membrane potential moves towards the E-Na

Question 4

What is the principle mode of action of the 2 main types of Na gate and hows does that affect the g-Na

Answer 4

The two main types of Na gates are activation and inactivation gates. Usually the inactivation gate is open at one end all the time. Once the threshold potential is reached the activation gate opens and g-Na is at maximum through the channel. However with the opening of activation gate the inactivation gate starts to close slowly (this is the key) so g-Na drops steadily with time

Question 5

Define threshold potential

Answer 5

When Na depolarizing current exceeds K repolarizing current

I-Na > I-K

Question 6

What is he trying to explain here

Answer 6

E-V(Na) decreases and E-V(K) increases during upstroke of action potential. It is important to know why is this as E-V is the driving force for the different kinds of currents in each cell

Question 7

What eventually ends the Na current

Answer 7

The inactivation gates slowly closing, when they all close that will eventually end the Na current

Question 8

Na inactivation gate curve

Answer 8

Question 9

What happens during repolarization

Answer 9

There is a decrease in g-Na due to the closing of inactivation gates that drives the membrane potential towards E-K

Question 10

Explain the mode of action of the 2 main Na gates from the point of depolarization to the point of complete repolarization

Answer 10

1. Inactivation gate is open, activation gate closed during rest
2. Depolarization causes the opening of the activation gate
3. The inactivation gate start to slowly close
4. The inactivation gate completely closes whereas at the same time the activation gate is also still completely closed
5. The final step of repolarization is the opening of the inactivation gate and now the cell is where it started

Question 11

This is an important slide. What is he trying to explain here

Answer 11

When we look at the graph it appears that when all the inactivation gates open the activation gates are closed and when all the activation gates are open the inactivation gates are closed. In reality this is not true since this curve only shows the steady state value of a gate at a certain electric potential. It does not take into considerations the kinetics of this reaction. Hence in reality there are times when both of the gates are open that allow Na to move in as the activation gates open much much MORE QUICKLY than the inactivation gates

Question 12

What happens if the cell is not allowed enough time to completely repolarize

Answer 12

Not all of the inactivation gates would be open (remember they are the slow gates) which causes the cell to have reduced fractional conductance to Na and hence this will impair the ability of a cell to generate a strong enough Na current during the next event of depolarization

Question 13

Explain the mechanism of action of K Delayed Rectifier channel

Answer 13

During repolarization g-Na decreases and g-K increase. This is partly achieved by the K delayed rectifier channel. It is important to know that this channel opens slowly which is important for repolarization as if it were to open at the same speed as the activation gate of the Na channel, K would exit out of the cell and Na will enter the cell the effects of both will be cancelled out.

Question 14

Structure of K delayed rectifier channel

Answer 14

Only has the activation gate, also remember that it starts to open during depolarization, not during repolarization as it CAUSES repolarization

Question 15

Answer 15

Identical to Na activation gates, note that activation Na gates are faster, this is not accounted for in this graph

Question 16

Know the curves for g-Na, g-K and the wave of depolarization-hyperpolarization

Answer 16

Question 17

Summary

Answer 17

Question 18

Define and differentiate between absolute refractory period and relative refractory period

Answer 18

Absolute: Once depolarization has occured, no stimulus no matter how strong will cause an onset of another action potential. This time period is called the absolute refractory period

Relative: during the time of repolarization, some inactive channels are being converted to resting channels. During this period a STRONGER STIMULUS can cause the generation of an action potential. This time period is called the relative refractory period

Question 19

What is the underlying condition of hypokalemia and hyperkalemia

Answer 19

Whenever a cell has an impaired ability to generate a sufficient Na current for depolarization, the cell’s ability to generate an action potential will be impaired and its excitability will be reduced (as a stronger stimulus will be required). This is what happens in hyper and hypokalemia

Question 20

What are the 2 essential priniciples for complete repolarization

Answer 20

1. Sufficient time
2. all the gates have to be completely open (inactivation-Na gates). This is the problem in hypo and hyperkalemia

Question 21

All or None law

Answer 21

If a depolarizing stimulus reaches threshold the resulting AP will have the same characteristics:

1. Amplitude
2. Rate of rise of the action potential

Assuming the conducatance and the number of gates for both Na and K remain the same

Question 22

The magnitude of depolarizing cuurent during the upstroke of action potential determines

Answer 22

1. Threshold potential (the magnitude of AP determines where the threshold potential is)
2. Amplitude of action potential
3. Rate of rise of AP
4. Conduction velocity of AP like the speed of AP down a nerve for example

Question 23

What happens when there is less I-Na

Answer 23

1. Threshold potential is more positive
2. Amplitude of AP is decreased
3. Rate of rise is decreased
4. Conduction velocity is decreased

It is important to know how each of these 4 are effected by I-Na (the curve in the red shows that)

Question 24

How can E-Na change

Answer 24

1. High intracellular concentration
2. Low extracellular concentration

Remember that V-E(Na) is the driving force of sodium current

Question 25

4 ways sodium current is reduced

Answer 25

Question 26

Hypercalcemia

Answer 26

1. Most common life threatening disorder associated with cancer
2. Occurs 10% to 20% of all cancer patients
3. Cancer cells release factors that releases calcium from the bones
4. Symptoms include muscle weakness, tiredness, confusion, unstable gait, constipation, decreased apetite, increased urination and bone pain
5. Serious complications include heart problems, convulsion and even coma

Question 27

What happens to sodium activation gate when there is hypercalcemia

Answer 27

Excitability is decreased, it is harder to fire action potentials and to generate action potentials

Question 28

What happens in tetany

Answer 28

The curve shifts to the left, there is more excitability

Question 29

What happens when the resting potential is moved more positive, what happens to the excitability

Answer 29

When the resting potential is moved more positive, it is closer to threshold potential. There is a decrease in the number of resting sodium channels and hence excitability is decreased. Hence threshold will be more positive while the amplitude and rate of rise of the action potential will be reduced, also the conduction velocity will decrease