Question about membrane potential

[Spirochete]

This question is the last thing that is bugging me about my basic understanding of a nerve impulse:

How can the there be a non-zero voltage across a membrane if the solutions on either side are electrically neutral? It seems like the existence of a gradient should necessitate at least one of the solutions having a net charge.

 

[Curious3141]

Nernst equilibrium. Search under that term - I've made a lengthy post about this before.

 

[Spirochete]

I read your whole reply below to the other thread. Unfortunately that college no longer keeps that physiology page up so I can't read the links.

So would it be correct to say that the two solutions on either side of the membrane are technically not neutral, we just speak about them that way because they're so close to neutral that it's really not significant, and the only important thing physiologically is the voltage?


The reason for your confusion is because of the simplistic, but erroneus way this topic is often taught in a school class. I was not even satisfied with what my standard med school physiology texts taught me about membrane equilibria, so I had done some research then. Of course, I've lost touch, but was able to refresh myself quickly with a bit of googling.

Read thru' these two links VERY carefully.

http://human.physiol.arizona.edu/SCH...t/14membra.htm

http://human.physiol.arizona.edu/SCH...t/15action.htm

The short version : the "real" reason for the resting memb pot of any cell is NOT the sodium-potassium pump (at least not directly). The real reason is something known as the Nernst equilibrium. Essentially, if you have a concentration gradient of a single ion between two sides of a semipermeable membrane that exhibits high permeability to that ion, you will get diffusion of that ion down its chemical gradient. But at the same time, that act of diffusion is accompanied by a gradually accumulating electrical gradient that opposes the movement. A point is reached where the electrical gradient will exactly counterbalance the chemical one, this point is called the Nernst equilibrium (NE). At the NE, no net ionic flux occurs and the membrane potential is stable. The NE is dependent on two things, the permeability of the membrane to the ionic species and the initiating chemical gradient. Interestingly, with a high chemical gradient and high permeability, the ionic flux required to swing a membrane from neutral to the NE potential is so slight that the original internal and external concentrations can be taken as not having altered. A lot of understanding of this whole thing hinges on that point : the actual concentrations are not really changing much at all. Rather, it is the *tendency* of movements to occur (which depends on changing permeabilities) that governs membrane potential.

The Nernst equation allows us to calculate the NE point for different ionic species. The combined equation for Na, K and Cl is the Goldman-Hodgkin-Katz equation. These two are explained in the first link I provided.

Essentially, for a resting cell, the memb pot is close to the Nernst potential for potassium. This is because the resting cell is far more permeable to K than it is to Na or Cl. The sole function of the active Na-K-ATPase is to establish the chemical gradient for K (and incidentally Na) with high K inside and low K outside. The natural leak of the K from inside to outside following this (due to high permeability to K) is responsible for causing the resting membrane potential. Just a small leak (relatively) is sufficient to establish the potential, as I explained earlier. If the pump is shut off and all else remains constant, the cell membrane will not go immediately towards neutrality because this is a stable electrochemical state (OTOH, the cell will take on water and lyse of course).

So it's now easy to explain what's going on with nerve cells. There are K channels always working in the cell that maintain the memb pot near the Nernst pot for K. A stimulus opens Na channels that moves the cell closer toward the Nernst pot for Na (which is positive). At a threshold pot, more voltage gated Na channels open up and the process is reinforced, the cell depolarises. Slower opening voltage gated K channels now start opening while the Na channels start closing, and the cell starts going back toward the K Nernst potential. At this point, the memb is even more permeable to K than in the resting state (because both the nongated and gated K channels are open) so the cell goes even further toward the K Nernst potential, resulting in the afterhypolarisation. The repolarisation toward resting memb pot is due to closing of the voltage gated K channels so that only the nongated K channels are open. The cell is now at resting memb pot.

Note the distinct lack of involvement of the active pump in the process of the AP and the aftermath - that's only involved in any residual cleanup and maintenance of osmotic pressure.

 

[Curious3141]

I read your whole reply below to the other thread. Unfortunately that college no longer keeps that physiology page up so I can't read the links.

So would it be correct to say that the two solutions on either side of the membrane are technically not neutral, we just speak about them that way because they're so close to neutral that it's really not significant, and the only important thing physiologically is the voltage?

Here's a wiki link that's more simplistic, but fairly good : http://en.wikipedia.org/wiki/Membrane_potential#The_Ionic_Basis_of_the_resting_potential

Strictly, the two solutions on either side of the compartment are not neutral, but they're very, very close to it. The net ionic flux needed to "set up" the resting potential is almost negligible.

 

[Jeff Corkern]

This question is the last thing that is bugging me about my basic understanding of a nerve impulse:

How can the there be a non-zero voltage across a membrane if the solutions on either side are electrically neutral? It seems like the existence of a gradient should necessitate at least one of the solutions having a net charge.

Here is what popped into my head.

You're confusing "electrically neutral" with "at the same potential." NOT the same thing.

There certainly is no difference in electrical energy because they are electrically neutral, but there IS a difference in chemical energy, which is expressed in a flow of electrons.

A plain old salt-bridge battery is PRECISELY the same kind of system. The two solutions are electrically neutral, but there is a difference in chemical energy, redox potential, and so a current flows.

Does this help?

Jeff Corkern
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"If people possesses immortal souls, it should be possible to deduce this by logical analysis of their behavior."

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[Spirochete]

While I admit I'm a bit shaky on redox potentials other than the fact that they're a measure of how much something "wants" to be reduced, and the fact that redox reactions generate energy. . .

I've never heard the concept of redox potentials being applied to the nerve impulse. Usually it's explained in terms of electrochemical gradients and how charged particles, usually cations, move in response to that gradient.

Are you sure that your example with the battery applies?

 

[Jeff Corkern]

While I admit I'm a bit shaky on redox potentials other than the fact that they're a measure of how much something "wants" to be reduced, and the fact that redox reactions generate energy. . .

I've never heard the concept of redox potentials being applied to the nerve impulse. Usually it's explained in terms of electrochemical gradients and how charged particles, usually cations, move in response to that gradient.

Are you sure that your example with the battery applies?

Now that I've thought about it---yeah, I'm sure. "Electrochemical gradient" is EXACTLY the reason batteries work. It's just that in batteries, there's only one chemical species in each half-cell that's being oxidized/reduced. In cells, it's a thousand times more complicated, but the fundamental reason electrons flow is the same. Oxidation/reduction.

I know a way you can test it.

Mix up a solution in a beaker that has the same chemicals in the same concentration as the INSIDE of a cell.

Then mix up a solution in a different beaker that has the same chemicals in the same concentrations as the OUTSIDE of a cell.

Then run a wire from a voltmeter to each and see if there's not a POTENTIAL difference between them.

Hmm. You seem to think electrons can flow only when there's a charge difference, a difference in the number of electrons in two places.

Not quite. The electrons will also flow when there's a CHEMICAL energy difference.

For example, let's consider what happen when you put a stick of Zn in a solution of Cu+2. BOTH IN THE SAME SOLUTION.

(For all you other chemists out there, yes, I'm skipping some details.)

What we start out with is Zn+0, zinc metal, and Cu+2. But that particular solution is at NOT its lowest potential energy point. There's a CHEMICAL ENERGY instability. What's actually more stable is a solution of Zn+2 and Cu+0.

And so the system in the beaker rolls downhill, down the chemical energy hill. A reaction occurs.

Zn+0 + Cu+2 ====> Zn+2 + Cu+0

Cu+0, copper metal, plates out all over the beaker, and the zinc dissolves.

Note this reaction is, fundamentally, AN ELECTRON FLOW. AN ELECTRON FLOW HAS OCCURRED FROM THE ZINC TO THE COPPER.

Right?

And because this reaction is fundamentally an electron flow, we can actually put the two reactants in DIFFERENT beakers---and the reaction will STILL happen! As long we put an electrically conductive bridge---SOMETHING THAT WILL CARRY ELECTRONS----between them.

 

[somasimple]

Hi Jeff,

If I can easily accept electro chemical potentials and your example where you create an electric circuit, I can't transpose it to a cell!
Where is the circuit? Where are the metals? What is the redox reaction used?
BTW, the existence of a membrane potential does not explain the propagation of nerve impulse.

 

[Cincinnatus]

Hi Jeff,
the existence of a membrane potential does not explain the propagation of nerve impulse.

Right, no one here has explained this yet. The original references that worked this out were the 5 Hodgkin-Huxley papers that were published in 1952. This is the body of work for which they won the Nobel Prize. These papers remain readable today and explain pretty clearly the line of reasoning that led us to our current conception of how an action potential works.

I may write up an explanation of the Hodgkin-Huxley model later, for now I'll just refer you to their papers which I'm sure can be found online for free...

 

[Jeff Corkern]

Hi Jeff,

If I can easily accept electro chemical potentials and your example where you create an electric circuit, I can't transpose it to a cell!
Where is the circuit? Where are the metals? What is the redox reaction used?
BTW, the existence of a membrane potential does not explain the propagation of nerve impulse.

The question wasn't how nerve impulses propagate. The question was how electrically neutral solutions could have a current flow between them.

It's not metals in a cell. At least as far as I know. I'm a chemist, not a cell biologist. It's more likely to be organic electron-accepting groups.

 

[somasimple]

The question wasn't how nerve impulses propagate.

Sorry but I read the first post =>

This question is the last thing that is bugging me about my basic understanding of a nerve impulse:

 

[cotarded]

There isn't any electron transfer - it's all ions establishing the charge (membrane acts as a capacitor for the separated ions).

The reason this happens with solutions that are electrically neutral can be partially demonstrated with the following super-unrealistic example:
Here's a membrane, left of the || is outside, right is inside:
10 X+ || 10 Y+ (X and Y are positive ions)
Okay, so we have an imbalance. If the membrane was equally permeable to X and Y, we'd equilibrate to this pretty fast:
5 X+, 5 Y+ || 5 X+, 5 Y+

But imagine it's only permeable to Y. In this case, if it were not for the electrical charges, it'd equilibrate to:
10 X+, 5 Y+ || 5 Y+.
But here is where it gets interesting. As the Y+ crosses from right to left, it creates a voltage potential across the membrane (acting as a capacitor). This voltage potential acts on the ions (though only importantly on permeable ones) creating a driving force. Eventually the driving force from the voltage gradient can oppose the driving force arising from the chemical gradient. At this point the ion reaches electrochemical equilibrium, even though it has not reached it's chemical equilibrium. This is what was mentioned above as the nernst potential, as you can calculate it pretty easily for a single ion with the nernst equation.

Hope that helps. I'll post back in a bit with a fun little problem involving biologically realistic numbers and maybe mention the Goldman-Hodgkin-Katz equation so we can estimate the membrane potential of a neuron from the intracellular/extracellular ion concentrations. Also, if anyone's interested, you can use the nernst potentials to see how changes in membrane permeability to different ions will affect the membrane potential (useful for seeing if even opening ALL the channels of a certain type will be sufficient to cause an action potential, or understand why on some neurons GABA causes depolarization *while* still acting as an *inhibitory* neurotransmitter).

lates,
cotarded
p.s. please mercilessly correct me on any errors/misleading wording/etc, I have no pretensions to expertise in this subject and am only trying to help.

 

[cotarded]

Oi, apologies, I got distracted and missed explicitly addressing the main point:

So would it be correct to say that the two solutions on either side of the membrane are technically not neutral, we just speak about them that way because they're so close to neutral that it's really not significant, and the only important thing physiologically is the voltage?

It is my understanding that almost all intracellular fluid, neuronal or otherwise, is negative with respect to the extracellular fluid because of the ubiquitous Na+/K+ ATP-ase and differential membrane permeability to Na vs. K (cell membranes are usually more permeable to K) (also, most proteins are anionic). But you can get a current without an initial electrical difference when electrically charged species move down their chemical gradient (as in my unrealistic example above where we had two equally charged solutions give rise to a voltage difference because of differential permeability).

blah blah,
cotarded.

 

[Cincinnatus]

Cotarded is correct, this is a good explanation of why we have a resting potential.