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

[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.

 

[somasimple]

They are not involved in maintaining the cell's resting potential. I don't see where you are going with this.

hHere or there =>
http://en.wikipedia.org/wiki/NaKATPase
http://advan.physiology.org/cgi/content/full/28/4/139

 

[Cincinnatus]

You are quoting me out of the context of the conversation.

In the short term, Na ions are flowing into the cell balanced by K ions flowing out. Several other ions are also crossing the membrane in this charge balanced manner. This and this alone is sufficient to maintain the resting potential for short periods.

In the long term, something else is necessary to move the ions back to the appropriate side of the membrane. These are the various pumps like the Na/K pump.

This explanations is consistent with the experiment you mentioned where lack of ATP leads to a loss of ion imbalance after a period of hours. That is, in the short term the Na/K pumps are unnecessary. After several hours without ATP (and thus without functional Na/K pumps) the concentrations of the ions becomes equilibriated and the electrochemical gradient is destroyed.

 

[somasimple]

About cable
http://www.st-andrews.ac.uk/~www_pa/Scots_Guide/audio/part7/page1.html
www.geocities.com/ve2_azx/CoaxialCableDelay.pdf
http://www.ivorcatt.com/4_6.htm
http://users.encs.concordia.ca/~trueman/bounce/demos.htm
http://www.st-andrews.ac.uk/~www_pa/Scots_Guide/audio/skineffect/page5.html

In the short term, Na ions are flowing into the cell balanced by K ions flowing out. Several other ions are also crossing the membrane in this charge balanced manner. This and this alone is sufficient to maintain the resting potential for short periods.

We are in the first milliseconds, and I want to know what happens to Na ions once they entered? The hypothesis is that ions channels are closed/inactivated. I contest it since the graph shows a high permeability/conductance! I do not care they are balanced. It does not change anything to my asking!

ps: The ohm law works with definite electrical circuits: Please, draw me one?

 

[somasimple]

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.

You're focused by results that are computations of integrations. That makes very good average values but... Averages are averages.

Ions cross membranes through ions channels! Do you expect that every ion get the same chance or velocity in this process?

 

[Cincinnatus]

We are in the first milliseconds, and I want to know what happens to Na ions once they entered? The hypothesis is that ions channels are closed/inactivated. I contest it since the graph shows a high permeability/conductance! I do not care they are balanced. It does not change anything to my asking!

What graph are you referring to here?

You're focused by results that are computations of integrations. That makes very good average values but... Averages are averages.

Ions cross membranes through ions channels! Do you expect that every ion get the same chance or velocity in this process?

The HH theory does not address what happens when a single ion crosses. The theory is phrased in terms of voltages, conductances and currents.

We have other techniques we can use to describe the motion of a single ion. Typically we do this by assuming the ion's motion is described by a Wiener process (Brownian motion). Then we can calculate the mean first passage time for the brownian particle to hit a channel, pass through the channel etc. You haven't explained why you think this should be relevant though.

You have been alluding to your own theory for some time. I agree with Andy, now it is time for you to tell us what it is... Though as per the rules of this forum, you may need to submit to the independent research forum. We can read it there though.

 

[somasimple]

What graph are you referring to here?

This one:
https://www.physicsforums.com/showpost.php?p=1824723&postcount=23

If the sodium channels are inactivated (and I agree that we see an "inactivation") then the conductance may fall towards 0, immediately. It does, quickly but it express a Na ions movement.

We have other techniques we can use to describe the motion of a single ion. Typically we do this by assuming the ion's motion is described by a Wiener process (Brownian motion). Then we can calculate the mean first passage time for the brownian particle to hit a channel, pass through the channel etc. You haven't explained why you think this should be relevant though.

I know that but they extremely simplify the reality... In fact, simplification is quite a mandatory process in theory generalization. The problem is that one may simplify the wrong fact.

You have been alluding to your own theory for some time. I agree with Andy, now it is time for you to tell us what it is... Though as per the rules of this forum, you may need to submit to the independent research forum. We can read it there though.

Too soon but I suspect you're interested...

 

[Andy Resnick]

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.

<snip>

Soma,

Firstly, I wouldn't say I am irritated, exactly. I choose to participate in this thread or not. At some point I will reach diminishing returns and drop out. Second, I'm not sure I would consider myself an authority on the subject, either. Hopefully I'm not merely quoting doctrine- I am trying to provide evidence.

 

[Andy Resnick]

<snip>

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?
...

I agree with the hypothesis that a channel can be open and inactive is an odd one; I also have problems with waving the magic wand of "conformational changes" to explain things. Nonetheless, I have nothing better to add and the concept has explanatory power- calmodulin, for example.

Rectifying channels, either inward or outward directed, are not so difficult to think about- I picture it as one reaction is favored over the other. For example, Na-K-ATPase can either consume ATP to transport ions against the electrochemical gradient, or can generate ATP by running in reverse- both can occur under test-tube conditions, but the forward reaction is (highly) energetically favored in a cell.

Note I haven't really drawn a distinction between a channel, a transporter, co-transporter, pump, etc. Conceptually, there's not that much of a difference- some are 'active' (requiring ATP), some are passive, some are modulated by some mechanism, etc.

Not sure what you mean by "water that fills the channels sequences"... there are water channels, and most ion channels are highly specific. Na+ and K+ are not the same size (different hydration radius), and that is the key to understanding the selectivity. The transit time for an ion across a 10 nm membrane, subject to a 60 mV driving potential, is likely to be small.

Where is the energy required to maintain the membrane potential? Better to ask where is the setpoint. How is the membrane potenial set to a particular value? What are the feedback and feedforward mechanisms to stably maintain the membrane potential?

 

[somasimple]

Not sure what you mean by "water that fills the channels sequences"...

The channel can't "pass" ions without water as you know. It has been confirmed by Prof R MacKinnon. These sequences (ion/water/ion...) may have profound consequences.

Where is the energy required to maintain the membrane potential? Better to ask where is the setpoint. How is the membrane potenial set to a particular value? What are the feedback and feedforward mechanisms to stably maintain the membrane potential?

I learned a lot from this site.
http://www.lsbu.ac.uk/water/kosmos.html
http://www.lsbu.ac.uk/water/cell.html

 

[Mike H]

We are in the first milliseconds, and I want to know what happens to Na ions once they entered?

You're focused by results that are computations of integrations. That makes very good average values but... Averages are averages.

Ions cross membranes through ions channels! Do you expect that every ion get the same chance or velocity in this process?

I haven't entirely been able to keep track of all of the details of this conversation (I napped through the neuro section of my one cell bio class as an undergraduate during the Clinton administration), but I can't but help wonder about a few questions after reading the above quoted material.

What is the status of single molecule methods as applied to ion channel function? As a physical chemistry/biophysics sort, I tend to think in terms of optical spectroscopic/microscopy methods, which - from the last time I was digging around in this topic - only gramicidin had been subjected to such investigations with any degree of publishable success. I've heard of such things as doing electrophysiological measurements on single ion channels - are the results from such measurements consistent with larger-scale measurements? My impression is that they are, but I know that drawing such conclusions can be a somewhat non-trivial affair.

I'm also curious as to what is meant by "what happens to Na ions once they enter" the cell. Do they not just hydrate and dive into the cytoplasm, waiting to be pumped out or eventually used as a cation to bind to some biological macromolecule in due time? I know that, for example, copper ions are carefully chaperoned after transport into the cell, but I was not aware of any suggested similar mechanisms for sodium.

somasimple - I would be very interested in reading your theory (although it looks like we'll have to wait for it), particularly if it involves any material not yet in the literature regarding kinetics of single ions being transported across a biological membrane (actual cell or model system) and/or being able to track single inorganic ions upon entry into a cell and their fate, esp. if there's an as-yet-unidentified sodium chaperoning/trafficking pathway.

 

[Renge Ishyo]

Soma, it is expected that the current would decay slowly over time after the channel is shut off. The reason why there is a "sharp" change at first is that the gradient was established prior to the opening of the channel (thus, this part of the cycle will not show on the graph anymore than it does on a discharge graph for a DC capcitor). After the ions flow in, in a short period of time there will be a lot of positive ions in the vicinity of the membrane and the Vm will be affected at its peak at this point locally on the membrane (but I should mention that it will affect only a very small area of the membrane as this ion increase is negligible at this point compared to the ion content in the cell at large). A brief time later if the channel is closed so that no more sodium ions rush in, the Vm in the vicinity of the membrane will gradually decrease back towards the predominating membrane potential in most of the cell all on its own. Why? It is because the ions are mobile and are in an aqueous solution. The sodium ions will diffuse away from the membrane, and the positive charge density will spread out as much as possible. This *slowly* dilutes the effect of the positive charge increase on that small region of the inner membrane over time.

This is the same thing as the "ocean diffusion" example given earlier; if the strong acid is dumped into the ocean and you are measuring this area with a pH meter, you will see an immediate "spike" to a pH of 1 after dumping. This would then gradually decay to the pH of the ocean as the hydrogen ions diffuse away from the place where the bottle was emptied.

The cell couldn't keep this up for ever (and neither could the ocean; in theory if I kept on dumping acid into the ocean like this, after a long period of time the pH of the entire ocean would eventually be altered). The long term accumulation of positive charges would build to a point to where the membrane potential of the entire cell was altered, and at this point the cells function would be altered. The Na/K pump prevents this "global" problem from taking place long term, which is why you can't shut it off forever and expect the ion gradients to survive indefinitely (although as you mention, it is reasonable to expect the gradient to hold up for some time before enough ions build up in the cell to change the entire membrane potential permanently).

Soma, I am confused as to which part of the theory you are questioning. Is it the mechanism by which the ion channel shuts off ion flow that interests you? Or is it the nature of an exponential decay of the residual current flow? The former is still being worked out and will likely need at least some knowledge of the protein structure to answer, but the latter would probably lend itself better to a physical analysis using diffusion based ion models and I don't see any clear reason why this model would have to contradict anything that came before it.

 

[somasimple]

I've heard of such things as doing electrophysiological measurements on single ion channels - are the results from such measurements consistent with larger-scale measurements? My impression is that they are, but I know that drawing such conclusions can be a somewhat non-trivial affair.

Thanks for the interest, Mike.
I already said that we need a simplification for a better understanding of the phenomenon.
The dynamics involved in a single realistic channel is far out of our computation possibility.
A single channel is unable to grasp the whole process, they work in a "collective" manner.
You need to simulate art least thousand and thousand of ions channels: I'm unable to do such a magical trick.
Here is a single ion channel within its natural environment.

 

[somasimple]

Renge,

I must thank you, once again to bring another subject of contradiction about membrane properties:

This marvelous membrane capacitor.
A single cm² that carries 1µF. That is clearly extraordinary and may make a furious envy to many electronics suppliers.
I attached a little piece of "membrane" it is only 0.5 µm long and has only 0.48 µm of diameter.
I put some ions channels on its surface with a reasonable density. Of course, it is just a point of view since it is too "regular" but it is the best arrangement for energy.

It looks like a sieve (and it is) but I may have some hard to fix a boundary of a single pFcapacitor.

Experiment:

1. Take a real capacitor http://www.interq.or.jp/japan/se-inoue/e_capa.htm
2. Charge it at will (It doesn't matter).
3. take a cm3 of saline water
4. put the wires into the water

Does the capacitor maintains any charge?
Does the water is polarized?

Second experiment:

1. Let the capacitor wires in the water
2. try to charge it (at will)

Have you any success?
Be careful and good luck!

I may have a similar reasoning with a resistor that works like an interrupter (ion channel).
The only possible solution is to insulate totally the wires from the medium => No wires => no circuit => no component => no current.

 

[Andy Resnick]

The channel can't "pass" ions without water as you know. It has been confirmed by Prof R MacKinnon. These sequences (ion/water/ion...) may have profound consequences.

I think Rod would be rather upset to hear his work so misrepresented- ion channels do not pass water. Read the history of aquaporin: prior to the discovery of the water channel, it was assumed that water diffused through the lipid bilayer.

Ions are stripped of their hydration shell upon entry into the channel; that is one reason they traverse the membrane so fast- to get re-hydrated on the other side.

I learned a lot from this site.
http://www.lsbu.ac.uk/water/kosmos.html
http://www.lsbu.ac.uk/water/cell.html

Ah- now I see what your motivation is. The water structure field is interesting, I suppose (I've read Pollack's book 'Cells, Gels, ..."), but there is no good experimental demonstration that requires structured water. Does it exist? Given the large field strengths present near a membrane, it would seem likely that the water is polarized. However, large-scale ordering of water molecules does not appear to exist.

 

[Andy Resnick]

<snip>

What is the status of single molecule methods as applied to ion channel function? As a physical chemistry/biophysics sort, I tend to think in terms of optical spectroscopic/microscopy methods, which - from the last time I was digging around in this topic - only gramicidin had been subjected to such investigations with any degree of publishable success. I've heard of such things as doing electrophysiological measurements on single ion channels - are the results from such measurements consistent with larger-scale measurements? My impression is that they are, but I know that drawing such conclusions can be a somewhat non-trivial affair.
<snip>

Single-channel patch clamping is reasonably routine here- it's tricky, to be sure- but really cool once it works. The data is usually a measurement of the open-channel probability as a function of whatever chemicals or votages are present.

In terms of optics, it's like dialing the intensity down and using a single-photon detector.

 

[somasimple]

I think Rod would be rather upset to hear his work so misrepresented- ion channels do not pass water. Read the history of aquaporin: prior to the discovery of the water channel, it was assumed that water diffused through the lipid bilayer.

http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/mackinnon-lecture.pdf

The K+ ion pair could diffuse
back and forth between 1,3 and 2,4 configurations (bottom pathway), or
alternatively an ion could enter the filter from one side of the membrane as
the ion-water queue moves and a K+ exits at the opposite side (the top pathway).
Movements would have to be concerted because the filter is no wider
than a K+ ion or water molecule.

I think too.

 

[somasimple]

Ah- now I see what your motivation is.

I do not understand the hidden sense of your sentence.
See references =>
http://www.lsbu.ac.uk/water/ref.html

 

[Andy Resnick]

I do not understand the hidden sense of your sentence.
See references =>
http://www.lsbu.ac.uk/water/ref.html

http://www.chem1.com/CQ/clusqk.html

 

[Mike H]

Well, now, I'm a bit more confused at this point. Probably should have paid more attention in cell bio way back when...

The dynamics involved in a single realistic channel is far out of our computation possibility.
A single channel is unable to grasp the whole process, they work in a "collective" manner.
You need to simulate art least thousand and thousand of ions channels: I'm unable to do such a magical trick.

OK, am I correct in understanding this as follows – the behavior of a particular single ion channel is dependent on its environment in the membrane, namely surrounded by many other ion channels? That is, there is some sort of collective behavior among many ion channels that is not observable by single channel studies, where a single ion channel of interest will have noticeable differences in its behavior whether it's alone or if it's surrounded by many other ion channels. This sounds perfectly reasonable to me in principle, but then I have to wonder something. It was stated earlier that

You're focused by results that are computations of integrations. That makes very good average values but... Averages are averages.

Ions cross membranes through ions channels! Do you expect that every ion get the same chance or velocity in this process?

If the important behavior to consider is of a collective nature (see the first quote in this post), why would it be important that not every ion might pass through the ion channel in exactly the same manner? You're interested in the collective effect of many ions passing through many ion channels, not just one ion through one ion channel. And why would it matter then that the Hodgkin-Huxley theory is one of averages and macroscopic/whole-cell behavior, and not single ion channels? Wouldn't it be rather appropriate then, as it describes (I'm figuring) the collective effect of many ion channels, which – according to the quote I have at the start of this post – is preferable to just focusing on a single ion channel which does not capture the full complexity of the process?

I understand the difficulties in carrying out large-scale biological simulations of membrane proteins and their surrounding lipid environment. However, I'm thinking that if the important effects only arise in the limit of thousands of ion channels (BTW, how firm of a limit is this threshold? Can you capture the emergence of collective effects for an ion channel surrounded by, say, 50 to 100 ion channels?), maybe a coarse-grained model based on more detailed single ion channel studies might be appropriate. That is, you plug the data/results from the best simulations you can run on a single channel into some sort of simulation where you're looking at a less-detailed array of many ion channels. I know people have done molecular dynamics studies on systems such as KcsA where they've simulated some of the bilayer and solvent, but I have the impression that sort of work is not directly relevant to the questions at hand.

Andy Resnick – Thank you for the response regarding single-channel patch clamping. It is greatly appreciated.

 

[somasimple]

I feel you're irritated there, Andy.

I do not "sustain" at any moment the content of your link.
Please, avoid the confusion.
I'm speaking about well known water bonds...

 

[Andy Resnick]

http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/mackinnon-lecture.pdf

I think too.

Ok, now we are getting somewhere. Again, this discussion would be a lot more efficient if you would simply put your ideas out there first, rather than requiring extensive back-and-forth to try and deduce your ideas.

From:

http://www.nature.com/nature/journal/v414/n6859/full/414023a0.html

'The structure sketched out the molecular basis of this specificity: a narrow 'selectivity filter' in the shape of an oxygen-lined electronegative tunnel in which dehydrated K+ (but not Na+) fits precisely. This structure rationalized why a K+ ion is so willing to leave its thermodynamically comfortable home in aqueous solution to enter the pore in a largely dehydrated form; the channel interior mimics the embrace of the water molecules in the inner hydration shell surrounding the ion in solution.

[...]

'Potassium ions are now seen in seven distinct sites along the pore-axis (Fig. 1a). Four of these reside in the narrow selectivity filter, and one in the wider hydrated cavity, as described earlier. By solving structures at varying ion concentrations, MacKinnon and colleagues argue that the four selectivity-filter sites are not all occupied simultaneously; rather, a pair of K+ ions separated by a single water molecule shifts in a concerted fashion between two configurations within the filter — inner and outer — occupying each about half the time (Fig. 1b).

[...]

'Most dramatically, in the position closest to the pore entrance a K+ ion is caught in flagrante, coordinated in front by four protein carbonyl groups reaching outwards, and behind by solvent; this must represent the long-postulated 'dehydration transition state' in which the ion sheds its water while entering the pore. It is now seen not to be a high-energy transition-state at all, but rather a true intermediate, an integral part of the flat landscape.'

This is all well and good, but I don't what this has to do with Sodium channels, which you consider to be the sole driver of an action potential spike, nor does it have to do with 'collective behavior' of thousands of channels, nor does it have anything to do with properties of lipid bilayers.

Consequently, now it's entirely unclear exactly *what* question you are trying to answer; we started with a discussion of the electrical dynamics of an action potential, to talking about sodium channel dynamics, and now you are discussing potassium channels.

Please take a moment to write out a coherent post discussing *your ideas*. Because right now I feel like I am chasing a moving target.

 

[somasimple]

Mikz,

Some numbers about the original experiments on the giant squid axon;

1/ its diameter is 0.5 mm => 500 µm
2/ its speed is 20 ms-1
3/ Action potential length is 40,000 µm => 40 mm.
4/ Surface of this patch is 62,800,000 µm²
5/ it contains 20,700,000,000 ions channels
6/ its circumference is 1,571 µm
7/ this circumference has an average of 28,535 ion channels.
8/ each slice of 1 µm contains 518,000 ions channels.

I said thousand and thousands...

Andy, you're picky there. We know that membrane has K and Na channels.

 

[somasimple]

Ionic contrast terahertz near-field imaging of axonal water fluxes.

Masson JB, Sauviat MP, Martin JL, Gallot G.

Laboratoire d'Optique et Biosciences, Ecole Polytechnique, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7645, Institut National de la Santé et de la Recherche Médicale U696, 91128 Palaiseau, France.

We demonstrate the direct and noninvasive imaging of functional neurons by ionic contrast terahertz near-field microscopy. This technique provides quantitative measurements of ionic concentrations in both the intracellular and extracellular compartments and opens the way to direct noninvasive imaging of neurons during electrical, toxin, or thermal stresses. Furthermore, neuronal activity results from both a precise control of transient variations in ionic conductances and a much less studied water exchange between the extracellular matrix and the intraaxonal compartment. The developed ionic contrast terahertz microscopy technique associated with a full three-dimensional simulation of the axon-aperture near-field system allows a precise measurement of the axon geometry and therefore the direct visualization of neuron swelling induced by temperature change or neurotoxin poisoning. Water influx as small as 20 fl per mum of axonal length can be measured. This technique should then provide grounds for the development of advanced functional neuroimaging methods based on diffusion anisotropy of water molecules.

PMID: 16547134 [PubMed - indexed for MEDLINE]

 

[somasimple]

Is the mobility of the pore walls and water molecules in the selectivity filter of KcsA channel functionally important?

Kraszewski S, Yesylevskyy SO, Boiteux C, Ramseyer C, Kharkyanen VN.

Institut UTINAM, Laboratoire de Physique Moléculaire, UMR CNRS 6213, Faculté des Sciences et Techniques, Université de Franche-Comté, 16 route de Gray, 25030 Besançon Cedex, La Bouloie, France.

We performed in-depth analysis of the forces which act on the K(+) ions in the selectivity filter of the KcsA channel in order to estimate the relative importance of static and dynamic influence of the filter wall and water molecules on ion permeation and selectivity. The forces were computed using the trajectories of all-atom molecular dynamics simulations. It is shown that the dynamics of the selectivity filter contributes about 3% to the net force acting on the ions and can be neglected in the studies focused on the macroscopic properties of the channel, such as the current. Among the filter atoms, only the pore-forming carbonyl groups can be considered as dynamic in the studies of microscopic events of conduction, while the dynamic effects from all other atoms are negligible. We also show that the dynamics of the water molecules in the filter can not be neglected. The fluctuating forces from the water molecules can be as strong as net forces from the pore walls and can effectively drive the ions through the local energy barriers in the filter.

PMID: 18404233 [PubMed - indexed for MEDLINE]

 

[Andy Resnick]

Mikz,

Some numbers about the original experiments on the giant squid axon;
<snip>

Andy, you're picky there. We know that membrane has K and Na channels.

Really...

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?

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?

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)?

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.

<snip>

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

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?

This is not really a discussion anymore- please put forth your ideas in a coherent manner now.