What happens to the Na+ ions during an action potential?

[somasimple]

Hi All,

It is a fact that Na+ ions cross the membrane and enter the cell during the rising phase of the action potential. The process happens because Na ions channels are open.
Then the ions channels becomes inactivated/closed for a while.

What happens to the Na+ ions that entered the cell?

 

[Renge Ishyo]

The sodium ions stay there for the time being until they are actively pumped back out of the cell by the Na/K ATPase pump.

What happens during an action potential is sodium atoms briefly flood into the cell down their concentration gradient which makes the inside of the cell a bit more positive than normal. To restore the membrane potential back to normal, potassium channels are opened shortly after the sodium ion channels are opened and potassium flows out of the cell down its concentration gradient (carrying its positive charge with it, hence putting the inside of the cell back to its original negative state after it leaves). The sodium is then pumped out, and the potassium is pumped back in using the ATP dependent pumps which completes the cycle.

 

[somasimple]

This explanation contradicts twice the facts:

1. Na K pumps are not involved in AP and it is a slow process.
2. The graph doesn't lie, the decay is also... fast.

 

[Andy Resnick]

Hi All,

It is a fact that Na+ ions cross the membrane and enter the cell during the rising phase of the action potential. The process happens because Na ions channels are open.
Then the ions channels becomes inactivated/closed for a while.

What happens to the Na+ ions that entered the cell?

Lots of things happen during an action potential- a transient regenerative spike in the resting membrane potential that changes from around - 60 mV to +20 mV. Some ion channels cause the spike, some channels respond to the spike.

The resting potential is caused by a concentration imbalance between sodium (high outside, low inside) and potassium (low outside, high inside) and is maintained by the Na-K ATPase combined with a potassium channel.

The action potential is caused by changes to the sdium and potassium conductance, leading to a small influx of sodium and efflux of potassium, corresponding to depolarization. It's important to note that small Na and K ion currents are sufficient to cause large changes in the membrane potential.

The channels that allow depolarization and repolarization are voltage-gated ion channels- channels do not use ATP to move ions, but allow passive diffusion of ions through the membrane as a function of the membrane potential. Hodgkin and Huxley,in 1952 using squid axons, generated a model system demonstrating how an action potential is generated by having voltage-gated changes to ion conductance.

Briefly, the rapid increase in sodium conductance causes the depolarizing phase as sodium influxes. Opposing this is hyperpolarizing potassium (and chloride) channels, which must be overcome in order to initiate an action potential. The delayed potassium conductance change is what brings about repolarization. Potassium channels determine the resting potential and terminate the action potential.

So the big picture is that the action potential is caused by movements of small numbers of sodium and potassium via ion channels.

Calcium channels are also involved, as they are also voltage-gated, and play a role in muscle contraction. There, the calcium influx causes calcium-mediated calcium release from the sarcomplasmic reticulum, which is then pumped back in by the SERCA pump.

 

[somasimple]

So the big picture is that the action potential is caused by movements of small numbers of sodium and potassium via ion channels.

I fully accept this explanation but if the rising is done by an influx then the decay must be done the same way in opposite direction (efflux) but all papers speak about Na ions channels inactivated or closed.
How is it possible to get a rapid decay when gates are closed?

 

[Andy Resnick]

Not all the papers. Have you read the original Hodgkin-Huxley papers? Potassium channels are a key player.

There are a few concepts required to understand what is going in:

1) reversal potential. This is the potential at which no ions flow through the channel.

2) Voltage dependence of the open probability. This is what is meant by voltage-gating

3) Inactivation of a channel. I don't fully understand this, but it means the channel is open but does not conduct ions.

4) channels can be rectifying channels- ions are allowed to move in one direction only.

The reversal potential of outwardly rectifying potassium channels (Shaker-type) is about -80 mV. The reversal potential of sodium channels is around + 50mV. The 50% open probability for K+ channels is around -30 mV, that for Na+ channels around -50 mV. The ~ 0% open probability is about -50 and -70 mV, respectively and the ~100% open probability is about -10 and -30 mV, respectively.

The voltage-gated Na+ channels produce the initial depolarization (ignore Ca+ for now). Shaker-type K+ channels are outwardly rectifying and also *delayed* in opening, and is responsible for repolarization. Now remember, the action potential is generated by changes in the *conductance* of a channel, meaning the open probability. The actual currents are quite small. The K+ channels, because of the low reversal potential, act to oppose the Na+ channel and maintain the resting state.

Again recall that small numbers of ions moving across the membrane will produce large changes in membrane potential: 0.004% of the K+ in a cell moving across the membrane will produce a potential of -61.5 mV.

 

[Renge Ishyo]

1. Na K pumps are not involved in AP and it is a slow process.
2. The graph doesn't lie, the decay is also... fast.

Perhaps the confusion here is caused by my sloppiness so let me clarify one point; the reinstatement of the Na/K gradients via the Na/K pump is NOT part of the action potential (as you mention). This part of the process happens after the fact.

The influx of Na accounts for the change in membrane potential and the efflux of K accounts for the restoration of the original membrane potential (as described in satisfying detail by Mr. Resnick in his posts above). I was including the Na/K pump as part of the description only to give the full picture of how the cycle works.

 

[Andy Resnick]

Renge,

I've never seen a reasonable discussion of Cl- transport in all this stuff: most of what I've read is that Cl- merely maintains cell volume (via osmotic balance). What's your presepective?

 

[Renge Ishyo]

From my understanding the Cl ion channel is somewhat of an oddity which is why it often gets completely bypassed in these discussions (it is sort of like that weird half brother that nobody likes to talk about...), but it does serve a purpose in the above process in that it can protect against overly negative membrane potentials (such as if too much potassium leaves the cell during the efflux after an action potential).

As with the sodium and calcium ions, Chloride ion is kept at a higher concentration outside the cell than that of chlorine ion inside the cell. But unlike the previous two ions, when the gate for this channel is open, chlorine ion moves spontaneously *against* its concentration gradient and even more chlorine flows out of the cell (it is for this reason that I believe it is usually ignored...its easier to ignore this behavior than it is to try and explain it, but I will do my best below ^^).

The only time this sort of thing can happen is when the membrane potential (Vm) is more negative than the normal desired amount (and my guess is the chlorine channel is not even opened unless triggered by this overly negative potential although I have yet to see this hunch "officially" confirmed). To see how this can happen, the formula that describes the Gibbs free energy criterion (or change in Gibbs, dG) for all of the above mentioned ion channel processes (borrowed from the text "Principles of Biochemistry" by Nelson, Cox) is:

dG = RTln(Cin/Cout) + ZF(Vm)

The logarithmic term in this equation describes the effect of concentration on membrane transport for ions. If the concentration on the inside (Cin) is lower than (Cout), as it is for sodium, calcium, and chlorine, then "RT ln (Cin/Cout)" as a whole will always be negative and ions will move spontaneously from a higher concentration outside to a lower concentration inside. However, this is not the only factor...the right term ZF(Vm) also determines the direction of ion flow. For chlorine, Z = -1...so in this case, if Vm is also large and negative then "ZF(Vm)" as a whole can be positive. If this term is positive and larger than the logarithmic term, then the movement will be against the concentration gradient and even more chlorine ion will move out as the Gibbs moves towards zero for the overall process.

This is how the chlorine ion channel works. The effect is much the same as the sodium and calcium channels (it makes the inside of the cell less negative). However, it does so by removing the negatively charged chlorine ions until Vm reaches the proper resting potential.

So then, the question might be "why bother with the chlorine ion channel? If the membrane becomes too negative, why not just let in more sodium and calcium to make things positive and normal again?" Well, it makes sense to do it this way as both sodium and calcium channels are directly part of the signal transduction process (as opposed to the potassium and chlorine channels which to the best of my knowledge merely transfer ions and not signals). Letting more of either sodium or calcium ions flow in could affect the membrane potential signal sent from these channels in a negative way (or have some other damaging effect such as creating unwanted additional signals to be propagated). In contrast, there is no action potential generated at the Chlorine ion channels, and so this channel allows the membrane potential inside the cell to become more positive without affecting the signal transduction process at all.

Or at least, that is my understanding of this at the present. Of all of the ion channels mentioned in this thread, the chlorine channel is by far the least studied of the bunch and may also serve some additional purpose that I am neglecting...

 

[somasimple]

http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000300005

I was extremely excited and honored when Guayo admitted me in his lab to work on my doctoral thesis. He first suggested measuring chloride fluxes during voltage clamp (36Cl was an isotope we could get, unlike 42K), but we found that their contribution to the resting conductance was quite small, indicating that in the squid axon the leakage current was mainly cationic.

The simultaneous measurement of ionic currents and fluxes allowed us to test directly whether Na currents were carried exclusively by Na after blocking the K currents. These experiments, done in collaboration with Illani Atwater, confirmed that the transport number of Na was, indeed, very close to one (Atwater et al., 1969) and also demonstrated that by interrupting the Na current before it inactivated, the large current tail also was transported exclusively by Na (Bezanilla et al., 1970a).

 

[Renge Ishyo]

Yeah Soma, we know these things (no need to bold!)...that's why I wrote in my post above:

...both sodium and calcium channels are directly part of the signal transduction process (as opposed to the potassium and chlorine channels which to the best of my knowledge merely transfer ions and not signals).

The problem is that your original question about what happens to sodium cannot be answered without considering what happens a short (very short) while *after* the signal has been sent.

I know the process as a whole is somewhat confusing, and I also know many Cell Bio texts (including the one that I read a few years ago) ONLY mention the sodium and calcium channels when talking about signal transduction and ignore discussion of the "cleanup" process involving the potassium and chlorine channels altogether (or they put the description of these channels in a completely different place)...my guess is this probably lies at the root of your original question about what happens to sodium after the action potential?

For a more complete view of the process that integrates the roles of the various channels into one discussion, I suggest having a look at the description given in the above mentioned "Lehningers Principles of Biochemistry" by Nelson, Cox (4th or I guess now 5th ed.) as it gives what I consider to be the most clear description of the interplay between all these channels that I have seen in a text (or at least it has a really good graphic of the ion channels, see Chapter 12).

 

[somasimple]

Well,
the K conductance is lower than the Na one and the number of K channel is 10 time lower than the Na one.
How is it possible that in quite the same time (because you excluded all other ions species) the voltage decays like it grew...quickly (but Na ions are confined inside and Na channels closed or inactive)?

 

[somasimple]

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=neurosci.section.201

The depolarization that produces Na+ channel opening also causes delayed activation of K+ channels and Na+ channel inactivation, leading to repolarization of the membrane potential as the action potential sweeps along the length of an axon

The delay makes trouble in a fast decay.

 

[somasimple]

For a more complete view of the process that integrates the roles of the various channels into one discussion, I suggest having a look at the description given in the above mentioned "Lehningers Principles of Biochemistry" by Nelson, Cox (4th or I guess now 5th ed.) as it gives what I consider to be the most clear description of the interplay between all these channels that I have seen in a text (or at least it has a really good graphic of the ion channels, see Chapter 12)

I ordered the book.

 

[Cincinnatus]

Somasimple seems to have some kind of axe to grind against the Hodgkin-Huxley theory of how action potentials are generated from electrochemical gradients and propagated down an axon.

Here is a previous thread on physicsforums where we discused this similarly: https://www.physicsforums.com/showthread.php?t=182840

If you google somasimple and action potential you will find many hits with him talking about the same things on many forums. As I recall when I looked him up last time, he had a long discussion about this on a wikipeda talk page as well.

 

[Andy Resnick]

From my understanding the Cl ion channel is somewhat of an oddity which is why it often gets completely bypassed in these discussions (it is sort of like that weird half brother that nobody likes to talk about...), but it does serve a purpose in the above process in that it can protect against overly negative membrane potentials (such as if too much potassium leaves the cell during the efflux after an action potential).

As with the sodium and calcium ions, Chloride ion is kept at a higher concentration outside the cell than that of chlorine ion inside the cell. But unlike the previous two ions, when the gate for this channel is open, chlorine ion moves spontaneously *against* its concentration gradient and even more chlorine flows out of the cell (it is for this reason that I believe it is usually ignored...its easier to ignore this behavior than it is to try and explain it, but I will do my best below ^^).

<snip>

Nice post- it took me a while to work through the whole thing.

My understanding (which appears to be similar to your explanation) is that movement of sodium or potassium changes the membrane potential not by adjustments to the concentration, but by movement of charge- that way small numbers of ions have a large effect on the membrane potential. Conversely, calcium movement does operate by concentration, because the intracellular Ca++ concentration is so low.

Chloride is intermediate- as you point out, the concentration gradient is small, so ions can flow either way depending on the details of the membrane potential. Plus, paracellular transport of Cl- is usually invoked to "complete the circuit" and maintain overall charge neutrality. So, just as the rule of thumb is that "water follows sodium", I guess "chloride follows charge".

I mostly work on the kidney- in the renal tubule, specifically the juxtaglomerular apparatus, Cl- is the rate-limiting ion for the Na/K/Cl cotransporter, which translates into a cell volume trigger back to the glomerulus: Increasing chloride concentration leads to a decrease in the glomerular filtration rate as a feedback mechanism for salt and water homeostasis.

Also, Cystic Fibrosis is purely a defect of cloride transport (CFTR). One hypothesis is that defective chloride transport leads to excessive and unregulated sodium absorption- it's not clear to me if the Cl- is absorbed or excreted- but the result is the same: dehydrated mucus, leading to problems in the lung and digestive system.

 

[Renge Ishyo]

Somasimple seems to have some kind of axe to grind against the Hodgkin-Huxley theory of how action potentials are generated from electrochemical gradients and propagated down an axon.

It is in the spirit of science to question things. My take is that so long as nobody kills or harms each other over differences in ideas then I see disagreement as a very very good thing (in fact, it is the horrible necessity of progress). Of course, people DO kill and harm each other over differences in opinion...so *ahem ahem*, in light of that observation, 95% of the time when I encounter someone with a different opinion, my response is to simply keep my ideas to myself. You would be amazed at how many times I have typed out these long posts here on PF only to delete them before posting, because I did not want to risk my ideas provoking a negative response in the person on the other end...

I ordered the book.

You will not be disappointed. I haven't had a chance to really look at the 5th edition yet, but the 4th did a better job on the cell bio topics than pretty much every other dedicated cell bio text that I have seen.

My understanding (which appears to be similar to your explanation) is that movement of sodium or potassium changes the membrane potential not by adjustments to the concentration, but by movement of charge- that way small numbers of ions have a large effect on the membrane potential. Conversely, calcium movement does operate by concentration, because the intracellular Ca++ concentration is so low.

Chloride is intermediate- as you point out, the concentration gradient is small, so ions can flow either way depending on the details of the membrane potential. Plus, paracellular transport of Cl- is usually invoked to "complete the circuit" and maintain overall charge neutrality. So, just as the rule of thumb is that "water follows sodium", I guess "chloride follows charge".

As for the role of chloride in osmotic processes, I am sure all these ions and their individual concentrations have to be very carefully regulated to ensure proper balance. As far as signal transduction processes go, I don't see osmotic balance as too much of an issue per say, because of the rapid way with which the concentration gradients are manipulated and restored to balance, and the small size of the concentration changes with respect to the cytosol as a whole. Certainly in the case of a defective ion channel (such as in CF) where balance cannot be restored properly and the mistake "piles up" over time, the importance of establishing osmotic balance for these channels becomes readily apparent.

As far as the movement of charge itself being the dominating force (at least for external plasma membrane ion channels) as opposed to concentration, everything I have read lately points to that idea being right on. In my understanding, the 2nd term of that above equation dealing with the impact of charge on the process is THE critical contributor to the functioning of the voltage gated ion channels that appear on the external plasma membrane (intracellular channels such as the calcium channel in the ER lack a strong membrane potential and can be an exception, which I will get to in a minute). This is further reinforced when you consider that chloride is generally NOT kept with a small concentration gradient (yes, one of the many puzzling things about it); in fact, in most cases the concentration gradient is the same for chloride as it is for sodium. For example, in squid axon sodium is 440 mM outside and 50 mM inside whereas chloride is at 560 mM outside and 40-150mM inside. Yet, it is known that at least in neurons, chloride moves against the concentration gradient in its ion channels. My thinking is that the concentration gradients are set up to create, maintain, and tweak the membrane potential while the rapid changes in the membrane potential itself (created by opening or closing channels a bit too long compared with the norm) control the actual movement of ions and initiate the main responses (this is sort of clouded by the fact that sodium has *both* an inward concentration gradient and an inward electrochemical gradient for it that together "push" sodium into the cell when its channel opens, prompting explanations to focus on either one or the other).

Indeed the sensitive membrane potential, and not concentration, now seems to be the main driving force for the proton channels used in the production of ATP, at least for eukaryotes (plants do seem to use the "old pH model" that gets taught in schools which I won't get into here). This became apparent once they found out that the eukaryotic membrane wasn't "hording" protons in a little comparment like it does for intracellular calcium or in plants, but that hydrogen ions were free to diffuse away from the plasma membrane and become diluted throughout the cytosol. It is like dropping a bottle of concentrated hydrochloric acid into the ocean (which I should mention here is something that nobody should do); ten minutes later, if you stick a piece of pH paper into the same spot of oceanwater you will get the pH of the ocean and not the acid. External pH cannot be the driving force in such a situation. Yet, protons are driven through the proton ion channel to make ATP just the same...so the conclusion was reached that it actually was the negative membrane potential (with a small effect in proton concentration differences) that largely seems to pull the protons in. Of course, if you gave that answer in your typical college class on a test you will probably be marked wrong (even if some of the more recent cell bio texts such as "The Cell" by Albert, Johnson, Lewis, etc. do implement this somewhat more modern view).

The steep concentration gradient for calcium can be an exception to this as calcium channels are also used on internal membranes (such as the ER) that do not have the same strong membrane potential as the external plasma membrane does. Thus, two additional things are done so that the concentration term can dominate in the Gibbs for Ca in this instance: 1) Calcium is kept in a small sealed compartment (preventing the "ocean diffusion" idea from above and keeping the Ca concentration in the region of the channel very high), and 2) the concentration of Ca in the cytosol is kept extremely low. Of course, calcium can also function with ion channels on the external plasma membrane, and I suspect that as with Na,K, and Cl channels that in this instance once again the membrane potential become the dominant force over concentration, even for calcium.

These sort of ideas about the electrical potential are out there now, but they do not seem to get the same amount of "press" as the concentration concept because concentration differences DO still contribute and it is simply much more easy to understand than a more full picture that takes into account electrical potentials from Physics (and hence, the poor poor chloride ion channel, which then runs counter to the "easy model" about concentration gradients and ion movement, gets regulated to the "zit" status as the tendency seems to be more about covering it up and hoping it will just go away rather than probing deeper into its function...).

 

[somasimple]

Somasimple seems to have some kind of axe to grind against the Hodgkin-Huxley theory of how action potentials are generated from electrochemical gradients and propagated down an axon.

Here is a previous thread on physicsforums where we discused this similarly: https://www.physicsforums.com/showthread.php?t=182840

If you google somasimple and action potential you will find many hits with him talking about the same things on many forums. As I recall when I looked him up last time, he had a long discussion about this on a wikipeda talk page as well.

Cincinnatus,

I ask questions that seem important for the science community and it seems true that often I do not get any response. That is strange. I pointed out some basic violations of physics laws and the "faulty" drawings were removed from wikipedia because my argument was sufficiently strong.

The question of this thread is of a similarly importance since sodium, that is a major contributor to action potential, enters the cell but do not go out before a long delay. That contradicts curves and curves do not lie. Na entered and just returned out. That is a lesson of conductances. If you make a derivation of the curve you obtain an internal shift immediately followed by an external motion.

The theory must be refined. I have a theory that explains the fact, have you one that may explains this?

I have many respect for Hodgkin and Huxley (the scientists) and they were pioneers in the domain and I remind some great words from them: Our theory is a very simplified way to explain how the things really happen. And it is true that some huge but necessarily truncations have been made because it wasn't impossible at the time to compute anything.
Remember that a single pico second of a realistic ion channel computation takes several hours... Actually!

 

[Cincinnatus]

Renge Ishyo, I read your recent post but I'm not sure how what you are describing is any different from our usual formalism for talking about these questions. That is, we calculate the reversal potentials of the various ions by the Nernst equation (or some variant thereof). Once you know the reversal potential and the concentrations of the various ions then for any voltage you know which direction the ions will be flowing. This is what you said a few posts up.

This much was known before Hodgkin and Huxley. Their contribution can be viewed as the extension of this same formalism to the case where we have voltage gated ion channels. That is, the permeability of the ion is a function of the voltage.

---
Somasimple, are you asking about the (mostly) k-channel mediated hyperpolarization that brings the membrane voltage back down after an action potential? Or are you asking about how the electrochemical gradients themselves are maintained? This occurs by pumps like the Na-K pump.

---
I like what you said about the chlorine channel "completing the circuit" and maintaining charge neutrality. The AMPA channel has a reversal potential very close to 0 mV because it fluxes K, Na and Cl with differing permeabilities for each.

 

[somasimple]

Somasimple, are you asking about the (mostly) k-channel mediated hyperpolarization that brings the membrane voltage back down after an action potential? Or are you asking about how the electrochemical gradients themselves are maintained? This occurs by pumps like the Na-K pump.

Neither the primer nor the later. I just want to know where the Na ions go when they entered the cell (since we suppose Na channels are closed/inactive). The Na/K pumps are too slow to reverse the situation and it is proved than blocking them do not implies an increase in internal Na+.

The Na conductance gives matter to reflexion but we are in a condition where ions fluxes are supposed constant by the GHK equation (but not realistic).

 

[Cincinnatus]

Neither the primer nor the later. I just want to know where the Na ions go when they entered the cell (since we suppose Na channels are closed/inactive). The Na/K pumps are too slow to reverse the situation and it is proved than blocking them do not implies an increase in internal Na+.

Well this depends on how much the internal Na concentration actually changes during an action potential. I don't have these numbers available but maybe someone else does?

It could be that the change in concentration is negligible with respect to the concentration gradient. If that is the case then the future firing of the neuron will be unaffected and there is no need to have some other process removing Na ions from the cell on a fast timescale. The slower Na-K pump is enough to maintain the concentration gradient over longer timeframes.

 

[somasimple]

If that is the case then the future firing of the neuron will be unaffected and there is no need to have some other process removing Na ions from the cell on a fast timescale

Yes but it will automatically affect the resting potential and you must see its growing with future firing. Experiment show that several thousand APs may occur before any change occur...

 

[somasimple]

Here is an image about the Na conductance:

 

[Renge Ishyo]

Renge Ishyo, I read your recent post but I'm not sure how what you are describing is any different from our usual formalism for talking about these questions.

Correct you are sir; these ideas are very well rooted in classical experiments and (though contested and often misunderstood) the ideas I have presented are hardly revolutionary (that is why I am referring to their presence in certain textbooks as opposed to research papers).

My descriptions are attempts to try and understand the wheel, rather then reinvent it (although my willingness to actually talk about the chloride ion channel may have led you to believe otherwise ).

 

[somasimple]

these ideas are very well rooted in classical experiments and (though contested and often misunderstood) the ideas I have presented are hardly revolutionary

You're welcome.

A theory that explains the underlying mechanisms of:

• refractory periods
• propagation without "passive spread"
• inactivation of Na channel
• branching, acceleration...

and respects facts and laws of physics may be of some interest?

 

[somasimple]

Well, is there some evidence about the Na/K pump? I found some evidences that disprove it but none that support it?

 

[Andy Resnick]

You're welcome.

A theory that explains the underlying mechanisms of:

• refractory periods
• propagation without "passive spread"
• inactivation of Na channel
• branching, acceleration...

and respects facts and laws of physics may be of some interest?

Soma,

Several times in this thread you have alluded to some idea you have but have yet to present it. I think it's time you at least presented what you have in mind, rather than trying to claim other (well-established, well verified, well studied) models are invalid.

 

[somasimple]

Andy,

I have a full respect to your position and it's sure that such a novice like me may irritate such authority like you.

BTW, I'm not sure that someone gave me a satisfying response about the Na within this thread. Of course, I have an explanation but I'm querying all current hypothesis to see if the wheel is not already turning.

Well studied?
Is there a plausible explanation about refractory periods? Only a simple affirmation => The membrane stays in a refractory state (how?)
How do you explain that Na channel becomes inactive after some delay? I brought a graph showing a high permeability during the falling phase => a high permeability contradicts a closed gate.
What is the mechanism that makes the propagation unidirectional? Yes, because the membrane is refractory! (How?)
The action potential is propagated with an electrotonic current! When this current happens?
Where is the energy to maintain the Na/K pump?
Where is the delay in the cable theory?
What about the water that fills the channels sequences?
Have Na and K the same speed or size?
How is it possible to a ion to make an instant translation?
...

 

[Cincinnatus]

Is there a plausible explanation about refractory periods? Only a simple affirmation => The membrane stays in a refractory state (how?)
How do you explain that Na channel becomes inactive after some delay? I brought a graph showing a high permeability during the falling phase => a high permeability contradicts a closed gate.
What is the mechanism that makes the propagation unidirectional? Yes, because the membrane is refractory! (How?)
The action potential is propagated with an electrotonic current! When this current happens?
Where is the energy to maintain the Na/K pump?
Where is the delay in the cable theory?
What about the water that fills the channels sequences?
Have Na and K the same speed or size?
How is it possible to a ion to make an instant translation?

Soma, have you tried playing around with the NEURON simulation environment that Hines and Carnevale wrote? Here's a link to their forum: http://www.neuron.yale.edu/phpBB2/index.php
You should be able to answer all these questions for yourself that way. For example, you can use their NMODL tool to change around the properties of the sodium channel making them as realistic or phenomenological as you like and you can see how this affects the properties of the membrance excitability, refractoriness etc.

You ask how the sodium channel becomes inactive after some delay. The Hodgkin-Huxley theory does not address this question. Hodgkin and Huxley simply modeled the sodium channel with an "inactivation" parameter fit from experimental data. However, you can replace their phenomenological model with a more realistic model incorporating what we know about the kinetics of the channel. There are many different states that the channel can be in, each associated with different permeabilities. We can define rate constants that determine how the channel changes states. For details on how to do this simulation check out the following books:

Johnston and Wu, Foundations of Cellular Neurophysiology.
and
Koch and Segev, Methods in Neuronal Modeling: From Ions to Networks,

The latter is a collection of articles describing useful methods that you could use in conjunction with the NEURON software (or any other programming environment) to examine these questions yourself.

The Johnston and Wu book is the "bible" of cellular neurophysiology from a quantitative perspective. I recall they have a chapter early on in the book that describes kinetic models of ion channels and discusses how this reductionist view recapitulates the Hodgkin-Huxley formalism.

For your questions about cable theory there is no better reference (to my knowledge) than Cristof Koch's book called Biophysics of Computation.

 

[somasimple]

Cincinnatus,

I'm already registered on their forum. I'm not in agreement with the NEURON software that is fully electric and thus unable to mimic a single ion.
BTW, this software doesn't respect any SPICE model...

About Na channel => Experiments shows this delayed "inactivation" => I do not contest a fact.

About a cable theory: Is a real cable functions with ions? Is an axon shows some inductance?

Just try to get an open mind and try to reply to the question for yourself:
If the entering Na ions create a passive current spread thus it means that every entering positive ion will be associated with an electron or a negative ion but this will contradicts the HGK computing and how the interior may be more positive as the ions enter since they are immediately balanced ?

 

[Cincinnatus]

Cincinnatus,

I'm already registered on their forum. I'm not in agreement with the NEURON software that is fully electric and thus unable to mimic a single ion.
BTW, this software doesn't respect any SPICE model...

I don't understand what you mean here. NEURON assumes almost nothing for itself. You can build in whatever you like. Its just an easy way to keep track of conductances ie. solve the partial differential equations of cable theory. You can build in the particular form of all the currents yourself. The only real thing that NEURON assumes is Ohms law.

I don't know why you would be interested in a single ion anyway. The movement of one single ion has a negligible effect on the membrane potential.

About a cable theory: Is a real cable functions with ions? Is an axon shows some inductance?

I think now that English must not be your native language. I have no idea what you mean by "is a real cable functions with ions?".

Just try to get an open mind and try to reply to the question for yourself:
If the entering Na ions create a passive current spread thus it means that every entering positive ion will be associated with an electron or a negative ion but this will contradicts the HGK computing and how the interior may be more positive as the ions enter since they are immediately balanced ?

Are you trying to argue that the Goldman-Hodgkin-Katz equation is not being correctly applied when we use it to calculate the resting membrane potential? However it has been experimentally verified at least for the squid axon the numbers are quite well known... You must be trying to say something else, but I'm not sure what.

 

[Renge Ishyo]

If the entering Na ions create a passive current spread thus it means that every entering positive ion will be associated with an electron or a negative ion but this will contradicts the HGK computing and how the interior may be more positive as the ions enter since they are immediately balanced ?

If the ion charge were immediately balanced, it is correct that no significant current will flow due to a membrane potential (concentration gradient movement would still take place somewhat), but it is known that this is not the case. The charge imbalance is created by the nature of the Na/K pump. Both Na and K ions have the same charge (+1), but the pump brings in only two K ions for every 3 Na ions it expels. Assuming that the chloride ion channels are kept closed to simplify the thinking, this means that a "net positive" charge leaves the cell every time the Na/K pump operates (leaving the inside of the cell necessarily more negative with an ion imbalance as per the law of conservation of charge).

Accepting that the Na/K pump is used to establish membrane potentials helps to explain a lot of things such as the rather large amount of energy the body reserves for using these particular pumps. It makes sense to have to use all this energy if the Na/K pump is needed to do something very important that each and every cell needs such as establishing the ion flow for that cell as is postulated by the current theory...it doesn't make sense to devote a lot of energy to this process if this pump merely serves some other minor purpose.

I have a full respect to your position and it's sure that such a novice like me may irritate such authority like you.

Any respectable scientist is going to go with well supported logical theories when they go about explaining the universe around them. Don't take it personally; it is part of our training to learn the benefits of approaching things this way. I am not against those theories being challenged at all (in fact, I find it exciting when some new wrinkle adds a new understanding to an old familiar concept), but I see *no reason* to disregard well established views *until* I see some experiment, observation, or explanation that forces me to do so. If you believe you have that explanation and observation that forces the issue go ahead and publish it. I will evaluate whether I need to readjust my views at that time.

 

[somasimple]

As mentioned by Renge, I will apply logic and its correlate;
"All things being equal"

Validity domain of GHK equation (and thus the HH model) ?

Several assumptions are made in deriving the GHK current equation:

* The membrane is a homogeneous substance
* The electrical field is constant so that the transmembrane potential varies linearly across the membrane
* The ions access the membrane instantaneously from the intra- and extracellular solutions
* The permeant ions do not interact
* The movement of ions is affected by both concentration and voltage differences

Membrane is homogenous ? NO
The electrical field is constant so that the trans membrane potential varies linearly across the membrane? NO
The ions access the membrane instantaneously from the intra- and extracellular solutions? NO

Exercise of Logic:
1/ I may apply the GHK equation even if the validity domain is rejected
2/ I can't apply a ionic current theory or the ohm law for the same reasons.

I take logically the second reply.

I don't know why you would be interested in a single ion anyway.

Facts:
Neuron cannot make a complex electrostatic interaction (That's not its domain).
ions are involved in Action potential.

Logic:
If NEUTON is unable to mimic a ion, it can't for millions.

I think now that English must not be your native language. I have no idea what you mean by "is a real cable functions with ions?".

I'm French.
A real coaxial cable is made of metal and it has electric properties;
inductance
http://en.wikipedia.org/wiki/Inductance
A real cable works with electric current (electrons). The atoms do not really move.
In an axon, atoms move from outside to inside.

 

[somasimple]

Renge,

Theory:
A Na/K pump functions all the time and maintains the ionic imbalance.

Facts;
When ATP is blocked the ionic imbalance is maintained for several hours.

Logic:

1. Na/K pumps work even if they are blocked.
2. They do not work all the time.

I take logically the second explanation.

When the Na/K pump reaches the "good" ionic level:

1. Na/K pumps continue to work
2. They stop.

I take logically the second take.

Just logic.

 

[Cincinnatus]

As mentioned by Renge, I will apply logic and its correlate;
"All things being equal"

Validity domain of GHK equation

Several assumptions are made in deriving the GHK current equation:

* The membrane is a homogeneous substance
* The electrical field is constant so that the transmembrane potential varies linearly across the membrane
* The ions access the membrane instantaneously from the intra- and extracellular solutions
* The permeant ions do not interact
* The movement of ions is affected by both concentration and voltage differences

Membrane is homogenous ? NO
The electrical field is constant so that the trans membrane potential varies linearly across the membrane? NO
The ions access the membrane instantaneously from the intra- and extracellular solutions? NO

These are all quite reasonable assumptions despite not being true "strictly speaking". The fact that the model predicts experiments quite well validates our choice of premises. If the model did not agree with experiment then you could look to the premises to see what went wrong. The fact that the model does agree with experiment tells us that the assumptions we made are ok.

This tells us that the inhomogeneity of the membrane is a relatively minor contributor to the value of the resting potential.

I'm French.
A real coaxial cable is made of metal and it has electric properties;
inductance
http://en.wikipedia.org/wiki/Inductance
A real cable works with electric current (electrons). The atoms do not really move.
In an axon, atoms move from outside to inside.

So what? I don't know a damn thing about these so-called electrons, who am I? a chemist?

To understand cable theory all I need to know about are currents, conductances and voltages. It doesn't matter one bit if the currents are caused by a flow of electrons or a flow of ions. In fact I don't even need to believe in ions to understand cable theory. The only notions I need are Ohms law and some idea of current as something that "flows".

Theory:
A Na/K pump functions all the time and maintains the ionic imbalance.

Facts;
When ATP is blocked the ionic imbalance is maintained for several hours.

Logic:

1. Na/K pumps work even if they are blocked.
2. They do not work all the time.


I take logically the second explanation.

When the Na/K pump reaches the "good" ionic level:

1. Na/K pumps continue to work
2. They stop.

I take logically the second take.

No one claimed that Na/K pumps work all the time. They are not involved in maintaining the cell's resting potential. I don't see where you are going with this.