Action Potentials and Membrane Excitability

Hello All,
 
Here are your questions: (As before, I have grouped together like-questions so that I can attempt to answer them all together).  First lets start with some left-over questions regarding membrane potentials/membrane excitability:

1. A. If the ATPase pump does not work....does that mean the concentration of sodium inside the cell increases resulting in depolarization?

Now lets say you increase the concentration of potassium outside the cell. This results in an decrease of Nerst potential or potassium but what does that do to the membrane potential? And with the same situation but switched with sodium how does affect the potential as well. 

The concentration of sodium inside of the cell does increase slightly, but that is not what leads to depolarization.  Depolarization, actually, is due to the increase in concentration of potassium outside of the cell.  Because the cell is MOSTLY PERMEABLE to potassium at rest, that is the ion that will mostly be moving.  As potassium moves out of the cell it increases the concentration of potassium outside of the cell (from where it was before if the ATPase pumps are not putting it back inside of the cell).  This increase in extracellular concentration, thereby decreases the driving force (slightly) for potassium to want to leave the cell.  This increase in concentration (for example from 3mM to 5mM) depolarizes the equilibrium potential for potassium.  IF the resting membrane potential as a whole is mostly dependent on the equilibrium potential for potassium (because the cell is mostly permeable to potassium at rest), then if the equilibrium potential for potassium depolarizes, SO does the resting membrane potential.

An change in sodium concentrations across the cell does not have this same effect.  Although the pump will not be moving sodium back out of the cell if it is not working, sodium (at rest) is not moving very much anyways because the cell is not very permeable to sodium.  Therefore, the concentrations of sodium do not change as much as those of potassium.  In addition, since the cell is mostly permeable to potassium, the resting membrane potential is mostly dependent on that equilibrium potential and not the equilibrium potential for sodium.  If, however, the sodium equilibrium potential became less positive as well (which would be the case if the intracellular concentration increased), it may have a slight effect on the membrane potential and not have such a great pull on keeping it away from the potassium equilibrium potential.

1. B. If sodium channels did not work...does that mean cell hyper-polarize since the positive ions of potassium are leaving the cell via concentration gradient?

I'm unsure what you are asking here, but remember the sodium channels are only open from a change in voltage (see #5 below for further clarification on that), allowing for sodium to come into the cell depolarizing it.  This, however, does not happen at rest.  What does happen at rest is mostly movement of potassium through the potassium leak channels.  This movement does cause the membrane potential of the cell to move towards the equilibrium potential for potassium.  

2.  A couple quick easy questions, what are the Ex for Cl- and Ca++?  I know that Na+ is +60 and K+ is -90.  I tried googling it but would get different answers. 

I'm happy to hear that google gives you different answers, because remember two things:  equilibrium potentials are SOLELY dependent on the concentration differences for the given ion across the membrane.  The reason Na+ is approximately +60 mV and K+ is approximately -90 mV at rest is because of their typical concentration differences in a neuron at rest.  These values will differ if those concentrations differ, which THEY DO in different cell types and when they are not at rest (which they hardly ever are physiologically).  However, at rest in a typical neuron the concentrations for Cl- and Ca2+ are both higher in the ECF and lower in the ICF.  Calculating with those typical concentrations we find an equilibrium potential for Cl- of approximately -70 mV and for Ca2+ approximately +100 mV.

Also, we say that the Vm is closer to K because of the leakage channels, correct?  I saw that the Ecl is -70.  Wouldn't the Vm be closer to Cl if that is true?  I am not sure if -70 is correct, hence the question for wondering what it is- but if it is -70, why would the Vm be closer to Ek?

Yes, Vm is technically in fact closer to the equilibrum potential of Cl-.  However, remember that Vm is the membrane potential that is dependent on the electrochemical gradients for a variety of ions (K+, Na+, Cl-, and Ca2+) with respect to their relative permeabilities.  We say that it is closer to K+ because that is the ion that the cell is MOST PERMEABLE to at rest and it brings the membrane potential towards its equilibrium potential.  We are referring to how the membrane potential is located in reference to the ions that the cell is permeable to.  At rest the cell is next most permeable to Na+ and then only a very little bit permeable to Cl- and Ca2+.

Now here are some questions specific to action potentials:

1. The last question about propagation of action potentials said that an action potential induced in the middle will propagate potentials in both directions. Does this mean for the reverse direction, the AP goes through the axon hillock into the cell body? From there does it stop or does it go on through the dendrites to the next neuron's terminal buttons?

Yes, the AP will indeed propagate through the axon hillock into the cell body.  Remember that an action potential is only named because of what is happening with the voltage-gated channels and ion movements that create it.  As there are no voltage-gated Na+ or voltage-gated K+ channels located on the membrane within the cell body the depolarizing charges will dissipate at that point within the cell body and down the dendrites.  If they stay around long enough they may be able to re-activate an action potential at the axon hillock to then travel the correct direction down the axon, but essentially these charges dissipate over that space.

2. Also, we were are talking about neurons in the arm, are they REALLY long or are there a bunch lining up together? I think this is why I'm having trouble visualizing the concept.

They are actually REALLY long (but not as long as those in the legs).  In anatomy when you are studying a neuron that neuron may have a number of axons within it, but each axon (if it is somatic for example) is a single nerve cell whose cell body is within the CNS (in the spinal cord typically) and it travels through the body and synapses onto a muscle fiber.  It truly is just like a wire that is going from the wall into the fan to make it work.  As we learned in the autonomic nervous system, however, those are 2 nerve cells lined up that synapse onto each other at the ganglion.

3. I had a question about action potentials. I know we mentioned that Na channels open, inactivate and then close. I was wondering when the inactivation to closing occurs? Is this the absolute to relative refractory period? Also, does this mean that at the apex of the AP (positive 30) the Na channels are going to inactivate or close? 

Is the inactivation of Na channels the reason for the action potential to "stop" and the opening of voltage gated K channels the reason for repolarization and hyperpolarization (due to "slowness" of the voltage gated channels)?

At the apex of the AP the Na+ channels are going from open to inactivated.  Repolarization of the membrane is due to the opening of the K+ channels.  At the apex, simultaneously the Na+ channels are becoming inactivated (stopping the membrane potential from changing any further) and the K+ channels open thereby repolarizing the membrane.  

Na+ channels open by a change in voltage, become inactivated if they are open 'long enough' (so that is time-dependent) and then go from inactivated to closed by a change in voltage.  The change in voltage to cause the Na+ channels to go from inactivated to closed is a repolarizing change that occurs during the repolarization phase of the action potentials.  This indeed causes the end of the absolute refractory period into the relative refractory period because the closing of the Na+ channels (from inactivated) determines how many Na+ channels are available for a subsequent action potential (allowing the absolute refractory period to complete and the relative refractory period to begin).

4.  Do gradient potentials subsequently lead to action potentials by reaching threshold? 

I am going to assume this is meant to say GRADED potentials and yes, it is graded potentials which summate at the axon hillock that will subsequently lead the membrane to reach threshold and the action potential to be triggered.

5.  Is the stimulus for the opening of Voltage gated channels do to Cellular Signaling/2nd Messaging?

No, as the name implies, voltage-gated channels are opened due to a change in voltage across the membrane.  Therefore, a difference in charges (ions) and the movement of those ions across the membrane thereby causes the voltage-gated ion channels to change their confirmation thereby causing them to open.  Cellular signalling or secondary messaging can modulate this activity, but it does not directly stimulate it.  That is the change in voltage.

6.  Are voltage gated k channels open during the absolute refractory period?

Remember that the absolute refractory period is when there can absolutely not be another action potential.  This is when the Na+ channels are all either open or inactivated and up until the time where enough of them are 'recovered from inactivation' (ie. moved from inactivated to closed) to be able to open from a new stimulus.  Therefore, during the time after the Na+ channels are inactivated and while the membrane is repolarizing (thereby causing the Na+ channels to begin to go from inactivated to closed), the voltage-gated K+ channels will be open, but not during the depolarization phase.  Refractory periods, both absolute and relative, are due to the state of the Na+ channels, but the state of the Na+ channel is effected by the state of the K+ channel.

7.  I'm still not clear on WHY Na and K don't reach their E's... In the notes section it said that as the potential rises or gets more positive, the inactivation gate shuts the Na channel. Does it do this right before the E is reached for a reason? Or am I messing up the info?

I'm not sure that there is a 'reason' why it does it just before E is reached, but that is certainly WHY E is not reached (the inactivation gate blocks Na+ from further moving through the Na+ channel).  It's really a 'chicken and the egg' conversation to ask why it was designed that way, but it simply does not reach the equilibrium potential for E because the channels become inactivated.

 

I'm equally as fuzzy on WHY the K doesn't quite reach it equilibrium...

In a similar fashion to something blocking Na+ from continuing to move across the membrane (discussed above), the K+ channel closing prevents further movement of K+ through the membrane that would bring the membrane potential to the equilibrium potential of K+.  

8.  In your refractory periods slide you refer to a high Pk. I was wondering if you could tell me what that means?

Pk = permeability for potassium.

9.  Does changing the intensity or the amount of a stimulus changes A) the amplitude and B) the frequency of an action potential? What are the factors affecting the amplitude and frequency of action potential in general, beside number of sodium ions and its available channels?

A) NO, the amplitude of the action potential is dependent on the number of channels and ions available.  

B) Sometimes.  The frequency of firing of the action potential depends on the frequency of the stimulus (of threshold or suprathreshold size), and so if there is an input of lots of graded potentials so as the stimulus stays above threshold for a long period of time, the action potential will continuously fire after each refractory period ends. 

This may be difficult to conceptualize, but hopefully after we cover the synaptic transmission lecture you will be able to put the pieces of the activation of one action potential down a motor neuron which can then activate an action potential in the skeletal muscle can happen.

10.  I was going over the action potential lecture and had a contradiction in my notes. I understand that Na-VG channels open in the beginning of an action potential. However, do K-VG channels open simultaneously as well or do they open closer to the peak of the action potential. I recall you saying K-VG channels take longer to open and close but was not sure when they open.

I see where this can be confusing.  The actual opening of the VGK+ channels is at the peak of the action potential, but the voltage which activates that opening is actually at the same voltage where the VGNa+ channels are activated to open.  The VGNa+ channels are very quick so just after the voltage that activates them to open they do, but the VGK+ channels are slower, so they take a long time to actually open after being initiated to do so.

11.  I've been going through some practice questions and I was wondering why the answer below would not be to reduce membrane resistance? Is reduction of membrane resistance only for action potentials? What exactly encompasses the length constant for a graded potential?

5) If you wanted to engineer a better conducting neuronal fiber there are a number ofvariables you will have to consider.  Which of the following adjustments would increase the chance that a graded potential could make it to the axon hillock?

a) reduce myelination

b) decrease fiber diameter

c) increase length constant

d) increase longitudinal resistance

e) reduce membrane resistance

 

A reduction in Axonal resistance would DEFINITELY increase the propagation velocity and likelihood that the graded potentials would make it to the axon hillock.  The length constant I did not cover at all.  It is a physical parameter component that measures the distance that the charges can travel without dissipating.  Therefore, increasing the length constant would mean that the distance that the charges could travel before they dissipate out of the neuron would increase, thereby increasing the chance that the graded potential would make it to the axon hillock.