Action Potential Generation Flashcards
At what membrane potential does the Na activation gates open
-50 V, which is the threshold potential
Is threshold a fixed value
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
Explain the initial steps of depolarizing current in terms of electrophysiology once the threshold potential is reached
- Both of the gates, the activation gate and inactivation gate for Na channels open
- Conductance of Na increases (gNa as well as fNa)
- Na ions as a result flow into the cell, this is depolarizing current, flow of current into the cell
- Membrane potential moves towards the E-Na
What is the principle mode of action of the 2 main types of Na gate and hows does that affect the g-Na
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
Define threshold potential
When Na depolarizing current exceeds K repolarizing current
I-Na > I-K
What is he trying to explain here
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
What eventually ends the Na current
The inactivation gates slowly closing, when they all close that will eventually end the Na current
Na inactivation gate curve
What happens during repolarization
There is a decrease in g-Na due to the closing of inactivation gates that drives the membrane potential towards E-K
Explain the mode of action of the 2 main Na gates from the point of depolarization to the point of complete repolarization
- Inactivation gate is open, activation gate closed during rest
- Depolarization causes the opening of the activation gate
- The inactivation gate start to slowly close
- The inactivation gate completely closes whereas at the same time the activation gate is also still completely closed
- The final step of repolarization is the opening of the inactivation gate and now the cell is where it started
This is an important slide. What is he trying to explain here
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
What happens if the cell is not allowed enough time to completely repolarize
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
Explain the mechanism of action of K Delayed Rectifier channel
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.
Structure of K delayed rectifier channel
Only has the activation gate, also remember that it starts to open during depolarization, not during repolarization as it CAUSES repolarization
Identical to Na activation gates, note that activation Na gates are faster, this is not accounted for in this graph
Know the curves for g-Na, g-K and the wave of depolarization-hyperpolarization
Summary
Define and differentiate between absolute refractory period and relative refractory period
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
What is the underlying condition of hypokalemia and hyperkalemia
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
What are the 2 essential priniciples for complete repolarization
- Sufficient time
- all the gates have to be completely open (inactivation-Na gates). This is the problem in hypo and hyperkalemia
All or None law
If a depolarizing stimulus reaches threshold the resulting AP will have the same characteristics:
- Amplitude
- Rate of rise of the action potential
Assuming the conducatance and the number of gates for both Na and K remain the same
The magnitude of depolarizing cuurent during the upstroke of action potential determines
- Threshold potential (the magnitude of AP determines where the threshold potential is)
- Amplitude of action potential
- Rate of rise of AP
- Conduction velocity of AP like the speed of AP down a nerve for example
What happens when there is less I-Na
- Threshold potential is more positive
- Amplitude of AP is decreased
- Rate of rise is decreased
- 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)
How can E-Na change
- High intracellular concentration
- Low extracellular concentration
Remember that V-E(Na) is the driving force of sodium current
4 ways sodium current is reduced
Hypercalcemia
- Most common life threatening disorder associated with cancer
- Occurs 10% to 20% of all cancer patients
- Cancer cells release factors that releases calcium from the bones
- Symptoms include muscle weakness, tiredness, confusion, unstable gait, constipation, decreased apetite, increased urination and bone pain
- Serious complications include heart problems, convulsion and even coma
What happens to sodium activation gate when there is hypercalcemia
Excitability is decreased, it is harder to fire action potentials and to generate action potentials
What happens in tetany
The curve shifts to the left, there is more excitability
What happens when the resting potential is moved more positive, what happens to the excitability
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
