Neurophysiology and Autonomic Nervous System

Hello All,

I apologize for the late posting of these questions, but know many of you are just now starting to look at this materials.  As you know, I am off-island for this week, but please feel free to contact me via email or on the blog and know that I will respond to your questions and concerns as soon as possible to ensure a fluid understanding of the information.  Keep up the great work everyone! 

Here are your questions:

1) I just had a question regarding the Nernst Equation. If the total answer has a negative charge does that mean the ion is going out of the cell?

The Nernst equation allows you to calculate the difference in charges that exist for a given ion across the membrane that would cause the ion to be at equilibrium.  This indicates if the inside of the cell would have a positive difference in charges or a negative difference in charges at equilibrium.  The only way to know if the ion will move into the cell or out of the cell is to compare the equilibrium potential (calculated by the Nernst Equation) to the membrane potential that already exists (that may be 0 mV if the membrane is not permeable to any ions).  The ions will move in the direction that that ion (given its charge) needs to move in order to bring the membrane potential from where it is to the equilibrium potential for that ion.

2) The first question I have an issue with is #4. If you can't open your voltage gated potassium channel which plays a role in repolarizing the membrane, wouldn't the end of phase 1 be more positive? I don't really understand how it could stay the same.

4. A certain drug has the property of preventing voltage-gated potassium channels from opening.  If this drug is applied to an axon, how will membrane potential voltages at the end of phase 1 and phase 2 of the action potential compare to those of the untreated axon?

	End of Phase 1	End of Phase 2
A	More positive	More negative
B	Less positive	Less negative
C	Same	More negative
D	Same	Less negative

PLEASE Remember with regards to these questions that, although I am happy to discuss them, they are NOT the CTL questions, but these are OLD CTL questions.  CTL does not stand by these questions in terms of appropriateness to preparation for the exam and therefore you should take these questions with a grain of salt.

Remember that the voltage-gated K+ channels opening at the peak of the action potential is only half of what is happening.  The other half is that the voltage-gated Na+ channels become inactivated.  Also, remember that is something that happens due to time.  This would not be effected, therefore, by malfunction of any voltage-gated K+ channels.  Therefore, the depolarization of the membrane potential would still come to a halt, but the repolarization would not occur.  So, due to this the amplitude of the peak will reain unchanged, but the repolarization phase (and therefore where the membrane potential would be during the hyperpolarization phase) would be much less negative. 

3) Question 12 I also didn't understand. The answer is supposedly that the membrane is only permeable to Cl, but if it was permeable to K, then K would move from the right to the left, taking with it a positive charge and leaving the intracellular compartment more negative. I don't understand why it wouldn't be both K and Cl.

12. The figure below represents a solution system at 37^oC with a membrane separating the two compartments.  What ion or ions was the membrane permeable to in order to create a membrane potential of approximately -60mV on the right with respect to the left?

A) Na⁺            B) K⁺            C) Cl^-            D) Ca²⁺           E)  Equally permeable to K⁺ and Cl^- 

F)  Equally permeable to K⁺ and Na⁺

This question is just like the third turningpoint question from the lecture.  The difference of that question, however, was that it indicated that the right side of the system was negative.  In this question, the right side of the system is more than just negative, but it is at a membrane potential of -60 mV.  If the membrane was only permeable to K+ as you indicate, the right side of the system would in fact be negative, but the membrane potential would be equal to the equilibrium potential for K+, that given the concentration differences in this system is not -60 mV (calculate it out utilizing the Nearnst equation).  The equilibrium potential for chloride, however, in this system IS -60 mV.  Therefore, if the membrane was solely permeable to Cl-, the membrane potential that would exist at equilibrium would be the equilibrium potential for Cl-, -60mV.
 
4) Lastly question 13. If the cell has a -70 resting membrane potential and you make it only permeable to Cl, wouldn't Cl want to both leave the cell to get away from the negative charge inside it as well as move into the cell down its concentration gradient? Therefore its electrochemical gradient would essentially have an arrow pointing into the cell for the chemical gradient and an arrow pointing out for its electrical gradient.

 

13.  The neuronal cell shown below has a membrane potential of -70 mV at 37^oC at rest.  When a chloride channel opens which of the following describes what happens (assume no other channels are open)?

A)  Cl^- will move into the cell following its chemical gradient hyperpolarizating the cell.

B)  Cl^- will move out of the cell following its electrochemical gradient depolarizing the cell.

C)  Cl^- will have an equilibrium potential more negative than the membrane potential.

D)  Cl^- will have an equilibrium potential equal to the membrane potential and Cl^- will not move. 

 

Remember that ions ALWAYS move in the direction that will bring the membrane potential towards THEIR equilibrium potential.  Therefore, YES, there would be a chemical gradient into the cell and an electrical gradient OUT of the cell, but the electrochemical gradient, the net of these two gradients, would be in the direction that the ions need to move in order to drive the membrane potential towards the equilibrium potential.  In this case, the equilibrium potential is approximately -60mV, therefore the equilibrium potential is in the direction that will bring the membrane from -70mV to -60mV and Cl- would, therefore, move out of the cell.

5)  What process underlies the refractory period?

I narrowed it down to 2 answers.

The transient inactivation of ligand gated sodium channels
or
The transient  inactivation of voltage dependent gated sodium channels

After looking through your powerpoint briefly, I recognized that it wasn't very specific. Mostly you just mention sodium channels in general open once it reaches threshold. Then, in a picture depicting the action potential, you show a channel in three positions, "open, closed or inactivated". In the closed position it appears as if a ligand is blocking the channel and preventing the passage of sodium ions. So why is it that the answer  is the voltage gated channel?

What process underlies the refractory period?

A) The delayed reactivity of voltage-dependant gated potassium channels

B) The slow functioning of Na/K ATP-ase

C) The absence of graded gradient 

D) The transient inactivation of ligand gated sodium channels

E) The transient inactivation of voltage-dependant gated sodium channels

  

That's a great question.  However, you eluded to the answer in your question.  You stated that the channel opens when the membrane reaches threshold.  The change in membrane that is occurring to have this happen is a change in membrane potential and THAT is a voltage change, making the channel voltage-dependent.  The 'ligand' that you are referring to in the figure, as I described in the lecture, is actually the inactivation gate and is part of this voltage-gated channel.

 

6) I wanted to confirm the answer to the last practice question we did in class(which I included below). The answer you gave as the correct choice was number 3.  I thought that action potentials only travel in both direction in skeletal muscle cells but travels in one direction in neurons. Also, answer choice 4 does make sense to me since myelin gives saltatory conduction and this is an increase in the conduction. Please advise.

 

Which of the following statements concerning the propagation of an action potential along a nerve cell axon is MOST ACCURATE?

 

1.       The rate of propagation of an action potential is faster in an axon of 10µm in diameter than in an axon of 20µm in diameter.

2.       The faster rate of propagation in myelinated axons is due to the highly conductive nature of myelin.

3.       A suprathreshold stimulus applied to the middle of an axon in the resting state will result in propagation of action potentials in both directions from the point of stimulation

4.       Myelin increases the propagation rate by increasing the conductance of the axoplasm.

You are correct that under typical conditions the action potential propagates in one direction down a neuron and can propagate in both directions on a skeletal muscle cell.  This is typical.  That is because the summation of graded potentials that occurs at the axon hillock activates the voltage-gated ion channels located there.  The depolarization propagates away from that space and can only propagate an action potential if there are voltage-gated ion channels.  These exist only along the axon and not within the cell body, therefore the action potential propagates in the single direction.  If, however, you had a suprathreshold stimulus activate an action potential in the middle of the axon, there would be no reason for the action potential to propagate away from that area and it would indeed propagate in both directions away from that point of stimulation.  This is precisely what happens when you hit your funny bone (ulner nerve).

Regarding the conductance, it does not increase the conductance of the substance within the axon (the axoplasm), but it simply allows for the charges to travel further within the axoplasm by increasing the space constant of this conductance, therefore that answer is actually incorrect.
 
7)In your slides, you posed the question, why doesn't the membrane potential reach Ena+ (after the na+ channels open and na+ rushes out).  Is it because the na+ channels are time-sensitive, and by the time they're inactivated not enough na+ has rushed out to raise the membrane potential that high... or is it because the k+ channels have kicked in by then, and they're bring the membrane potential back down?

That's a great question, but it appears that it is BOTH.  The Na+ channels inactivate at typically the exact time that the K+ channels open.  Therefore, if the Na+ channels did not inactivate, the peak of the action potential may be at a slightly higher membrane potential.  In addition, if the K+ channels did not open, the repolarizaiton phase would simply not start quite as quickly, but the membrane potential would still not reach the equilibrium potential for Na+.

8) Are the three stimulus types (subthreshold, threshold, and suprathreshold) types of graded potentials?

Even though suprathreshold stimuli are greater in magnitude than threshold stimuli, thus resulting in APs occurring more quickly, how do you actually know if it is a suprathreshold stimuli as opposed to threshold since both result in APs occurring?
Is it just a matter of measuring and comparing the amount of time it takes to reach the threshold membrane potential to generate the AP that can help to distinguish between the two?  So if it is a suprathreshold stimuli, it will push the membrane potential up to and past the threshold potential, so the amount of time it takes to initiate the AP is faster than a threshold stimuli, therefore distinguishing the two?

Indeed, those are types of graded potentials.  They are definitive changes in the membrane potential and describe what type of change occurs.  If a suprathreshold stimulus activated an AP, you would have a very difficult time determining if it was a suprathreshold or threshold stimulus, but the size of the membrane potential change due to the graded potential is what is defined as threshold or suprathreshold.  Indeed, the speed with which the membrane is brought to threshold can be one of the defining factors of these two different types of graded potentials.
 
9) 3.  If at rest parasympathetic activity dominates autonomic outflow.  Therefore, the intravenous infusion of hexamethonium, which causes the block of nicotinic acetylcholine receptors (nAChR), will cause all of the following will occur except which?

  A.  Heart rate will increase

  B.  Blood pressure will decrease

  C.  Airways will dilate

  D.  Digestion rate will decrease

--> I do not understand this question because from what I understand nicotine ACh receptors are on the preganglionic terminals of both Para & sympa thetic pathways...so if you are at rest and parasympathetic is dominating, and you block those receptors, would you switch to be sympathetic?  If not...doesn't blood pressure and digestion happen during the same pathways?

Indeed, because the parasympathetic is typically 'on', turning off the activation of both pathways would make it 'appear' that the sympathetic pathways are turned 'on'.  Therefore, an increase in sympathetic-like activities will occur including an increase in heart rate, dilation of airways, and the decrease in digestion.  Blood pressure, however,  will remain mostly unchanged or may increase slightly with the increase in heart rate.
 

10) For question 14 of the CTL, why is the answer constricted pupils and not excessive watery salivation, or both? I thought that parasympathetic innervation would lead to both.

Indeed, the arrector pilli muscles of the pupil and the activation of watery salivation are both activated by parasympathetic activation.  However, the facial nerve, that innervates the gland responsible for watery salivation, exists the spinal cord above C6-C7.