Action Potential Questions - (Feb/06/2006 )
Hi there,
I have a few questions about action potentials. Thanks in advance for your responses.
i) When a membrane is depolarized, there is a corresponding outward gating current. What actually causes the gating current? Why is it outward initially when the gate opens and inward when the gate closes?
ii) When temperature increases, the amplitude of the action potential decreases. What is the primary reason for the decrease?
I believe the decrease is being caused due to reaction kinetics. At higher temperature, reactions happen faster. Thus, the sodium channel gates opens and closes faster. This limits the amplitude of the sodium conductance and thus the corresponding decrease in the action potential amplitude. Am I over looking something?
iii) What limits the voltage gated potassium channels?
How do these potassium channels open and close? The opening seems straightforward - the depolarized membrane voltage causes it to open. But why the delay in its opening at the mechanistic level? And to what extent do these channels open? If we have a higher AP peak voltage, is there a corresponding increase in potassium conductance to decrease the membrane voltage?
I think there is an increase, but I don't understand what triggers the increase. Is it that more channels are opening due to the higher peak? If that's so, eventually it'll plateau since there are only so many potassium channels right?
Also, what triggers its closing? Is it because of a hyperpolarized membrane voltage or something else entirely?
Thanks very much for your responses agin.
Thean.
hi
for the first question, go in any book of physiology and do a little of osmolarities.
you sem to forget that depolarization automatically open (if not an inhibitory period is in course) the channels... there is in most of channel a proteic subunits that acts as voltage sensor...
as there are ion traffic during the potential, equilibriums change and membrane voltage too. As in depolarization, the votage ensor drives the closing of the channel...
you need to read more. 
I am with Fred_33 you should research a little more on your own... we aren't here to do homework, but will help if it is clear you have done your own research... along those lines you may know more than you posted, and it is more likely that you will get help if you show you already know these things... because I think you have tried some, and I like this topic, here are some hints...
think about the Na-K ATPase and how it works... Think about where the ions are before and after each action potential--draw yourself a picture that may help alot... Use your textbook or NCBI books to answer your third question, that is important, you need to know how voltage gated channels work--fred_33 also gave many good hints, be sure to also pay attention to the "inhibitory period" he mentions...
Good Luck... Try us back with more detail if there is something specific you don't understand...
I do appreciate and understand your desire that the poster do some research before blindly asking questions. Be assured that I have done some research. Possibly my questions needed further elaboration.
The answers you've provided, though accurate, don't actually serve to clarify the question. (I am greatful for the responeses though. It is not often that you get responses this quickly). So, allow me to rephrase.
i) There is an outward gating current, and we know it is caused by some 'particle' that is moving due to the depolarization. But why is it outward? Is it because the particle that's moving is inside the cell membrane, and its movement causes a charge imbalance to occur. Thus the outward current to bring back the balance. I suppose I was asking for confirmation of this. The books I've read do mention the gating current, but sometimes its nice to have confirmation.
iii) From HH's voltage clamp experiments using TTX, we know that the potassium conductance remains high as long as the membrane is in a depolarized state. We also know that the voltage gated potassium channels eventually close. The books I've looked at don't go into detail on how the potassium channels close. They mention sodium channels however. But thanks for your suggestion, I will look at NCBI to see if they explain the mechanisms involved in the potassium channel closing.
ii) The temperature effects on AP are actually documented by one of the experiments done by H&H. But they speak in terms of 'm' and 'n' the kinetic constants. I was trying to get an actual feel for the mechanistic process that causes increase in temperature to decrease AP peak. The books I have referred to usually speak in terms of these constants instead of explaining temperature effects in simple ion movement terms.
Thanks for your help! I look forward to the responses.
Thean.
gating current is not directional, it spreads in all directions, but the directionality comes into play because the upstream sodium channels are in a refractry period and don't respond to the new depolarization signals so only downstream channels open leading to a directional signal... if you were to initiate an action potential in the center of an axon it would spread in both directions -- this is what I meant about fred_33's "inhibitory period" hint.... The whole movement is dependent upon the fact that there is an imbalance of sodium and potassium ions on the inside vs outside fo the cell this is maintained by the NaK ATPase... A very important enzyme in all types of cells... see information from
http://images.google.com/imgres?imgurl=htt...hl%3Den%26lr%3D
The voltage-gated potassium channel works exactly like a voltage-gated sodium channel it just has a higher threshold (why it opens later) closes for the same reasons (as mentioned by fred_33)
I had understood that there is an all or none phenomenon with action potentials, if there is a temperature effect it should be a small one, and I did not know it... maybe someone else can address this question...
Hope that helps you...
I had understood that there is an all or none phenomenon with action potentials, if there is a temperature effect it should be a small one, and I did not know it... maybe someone else can address this question...
Hey,
Thanks for your response. I think we're talking about two different things here. The gating current, though it has to do with action potentials, actually doesn't have anything to do with inhibitory periods directly.
If you go through the Hodgkin and Huxley papers, he mentions the existence of a small current due to movement of the charged gate. Movement of a charged particle is the definition of current. That was his reason behind this proposition. He proposed that since the gate has to move outward (since it can't go through the membrane), the inside negativity of the membrane will slightly decrease. This will result in a small current (almost like capacitive current) to balance it. However, the events in an action potential sort of open the flood gates and there is a strong outward current resulting in the depolarization.
Due to the crude (by our current standards) instruments Hodgkin had, he wasn't able to see this small current. Studies in the 60s or 70s have shown the existence of this small current using patch clamping. In fact, regardless of the position of the membrane, this small current is always seen when the gate opens and when it closes. The book "From Neurons to Brain" has a good description of this. My question was, was the current caused by the gate moving or by some other mechanism in the operation of the voltage gated sodium channel.
I appreciate your point about the Sodium and Potassium pump. In terms of conservation of the coding, there are great similarities between the pump. But there are some important differences between the Na and K pumps. For example, the Na pumps go through the activation, inactivation and de-inactivation phases. While the K pumps activate and de-activate. I was curious about the mechanistic reasons behind this. I agree that going through the primary literature is the best way, but there are so many and when you have limited time, asking someone else sounds like a good idea.
Regarding the temperature effects, it is actually quite pronounced. Hodgkin noticed the temperature effects with his initial experiments. This, along with other things, resulted in a third degree function for modelling the conductance of the the sodium channel. I haven't taken Chemistry in a long while so I don't know what that means at the ionic level, just at the mathematic level. Thus, my question about what does it actually mean.
Thanks for your response and I look forward to continuing this discussion.
Thean.
Well Thean Vah, I really am sorry that I ever thought you hadn't researched your question, you are definately on top of this subject...
I understand what you are talking about, but I do not know about the movement of the voltage dependent channels, only very general terms... in fact I think that the mechanism of action for most of these channels may still be being investigated, at least the lab at the end of my hall does some computer modeling about the selectivity of these ion channels so I think it is not completely understood yet... your analysis is correct though it could be the charged amino acids that form the actual gate that move or some other charged aa perhaps peripheral to the gate/part of the voltage sensor? I don't know enough about the structure or mechanics to know... Try looking for a recent review about the structure of these channels maybe that will help some?
I had misinterpreted your question as the simpler one that I answered (thinking that outward meant out/away from the body of the neuron...) I am nit picking here, but the Na+K+ ATPase is a pump b/c it uses energy (ATP) to move the ions against the gradient, the voltage gated ion channels use this gradient and open to allow the ions to move passively (with the gradient/doesn't require energy) so they technically aren't "pumps" (of course this is just as far as I know-which isn't much 
)--not a big deal just being picky
The temperature effect is interesting, knowing how ions move through these channels and how they work may also help with this question? Sounds to me like you mean there is an all or nothing phenomenon that triggers the action potential but that the strength of the action potential can be changed based on temperature??
I don't know how much more I can help, but if you get information that you want to work through with someone I would be interested, maybe we can come up with some hypotheses if not answers...
good luck!!