Tom;
Thanks a bunch for the tips. You referred me to Kandel, Jessel,
and Schwartz's PRINCIPLES OF NEURAL SCIENCE, and that is the book
I have before me, and the book about which I have questions. You say
that a lot of terms are used, but that E and V are the same for the
biologist, that a bit of history is involved here, that one must go to
the original historical context and papers to make sense of it all,
but that E and V are the same for the biologist. And that is just
what I have questions about. Is the assumption justified?
Considering the historical context I can only conclude that the
assumption is not justified.
All through the nineteenth century and into the first part of
the twentieth century electricity was thought of as a fluid, and it
was figured that the laws of fluid dynamics were directly
applicable. The Nernst equations were developed by Walter Nernst
two decades before a term, 'amperes', was even agreed upon for I as
in V = IR; a decade before the discovery of the electron; more than
two decades before the place of the electron was understood in the
molecule. Nernst included the term 'valence' in his equation, but for
him valence was the tendency to be attracted to one pole or another
in an electrolyitc solution based upon the sign of the ion. Ions in the
1880's and 90's were finally widely accepted, along with atoms and
molecules, by chemists as things that really existed rather than
theoretical postulates. It would still be more than a quarter of a
century before Mendeleev's 1865 periodic table of the elements
could be understood in terms of electron 'shells', and longer still
before Pauling's 1939 treatise on the nature of covalent and ionic
bonds. Submolecular chemistry was poorly understood by the
chemist until then, and this ignorance was manifest in the
chemotherapy of Paul Ehrlich who searched for a 'magic bullet' early
in the twentieth century based upon the results of inductive, time-
consuming trial-and-error. The valence of Nernst is not the valence
of Pauling or that of electomagnetists speaking of the movement of
electrons in a conductor involving the valence shells of the
conductor's electrons traveling at near the speed of light.
It was theorizing about the electron which lead in the 1930's
and 1940's to the view that it was fundamentally different from any
fluid, it exhibited wave/particle duality and field effects and
traveled at near the speed of light on a wire. This was unlike any
ion, certainly. The four fundamental forces of nature were defined
as the strong force, the weak force, electromagnetism, and gravity.
The first two dealt with atomic nuclei; the third with light,
magnetism, electricity, and particles exhibiting a wave/particle
duality; and the last, gravity, with everything else including fluid
flow even of ions. Gravity dealt with bodies extended in space, not
point charges. Nernst was heavily into thermodynamics which
sought to explain heat in terms of atomic or molecular kinetics, a
helpful explanation, but no way near the modern day view of heat as
light or photons given off as electrons drop to lower energy levels in
the atom. So I must conclude, Tom, that history casts suspicion on
the idea that Em = Vm even if the units of measure are the same.
You write, "It's charge separation, baby. It's all charge.
Whether you're dealing with x mol of electrons separated by y
distance, or x mol of Cl- separated by y distance, it's all charge.
Remember, voltage is a measure of potential energy. That's all it
is..."
I agree with this, but there is quite a difference between the
potential difference of bodies extended in space and that of the
electromagnetist who deals with electricity. The first potential
difference is that of the fundamental force of gravity, the second
potential difference is that of electromagnetism. I think the trouble
I am having has its roots in the elision of these two different
subject matters.
You write, "A concentration gradient is potential energy.
(letting a chem flow down its gradient can perform work) A charge
separation is *also* potential energy."
Sure, I can go along with this, but again they are two types of
potential energy involving two different fundamental forces of
nature even if the unit of measure, volts, is the same. We're not
talking about the same thing. What I would like to know is what is
the justification for equating Ex with Vm; I am not content to take
it on authority because there are some problems with reason and
physics if this identity should be allowed.
You write, "If we have a membrane and we put different
concentrations of an ion on both sides, that ion will want to move
down its gradient. So will any other ions involved in the system."
Okay. But what makes this happen is entropy, not the doing of
work or the expenditure of energy, but the loss of energy to the
overall dissipation and 'disorderliness' of the universe. If we see
this Nernst potential as the amount of stored work in producing the
gradient, that says nothing about our ability to take this work out of
storage by letting the gradient run down. It's entirely a statistical
thing. Someone is taking the potential difference idea too far. If it
were so then why isn't power also derived at hdydroelectric plants
from the movement of the ions as the ion current goes by? Because
there is no stored difference in charge? Check out the types of ions
that coexist internally and externally in the squid giant axon.
Negative ions coexist with positive. So, the more polluted the water
the more ion current, and therefore the bigger the resevoir of
potential energy to be mined? Sound absurd? No? Too bad.
You write, "If we punch a perfectly selective hole in the
membrane that *only* lets Na flow through, we see it flow down its
gradient. It also builds up charge on the side it's flowing into. So,
we are converting the potential energy of the concentration
gradient into the potential energy of the electrical
gradient."
Here I have to disagree. You're saying that entropy, the running
down of the ion gradient, is just a change of potential energy from
chemical to electrical? If the concentration seeks to balance
through the hole we've punched, then the charge too is going to be
the same per unit volume on either side. There is no charge gradient
unless there is a density difference per unit volume, and that is
chemical concentration, not charge difference. The Nernst equations
are about ion concentrations, not electrical charge. We can only be
talking statistics here for the signs of the molecules of Na remain
the same as they flow through the hole.
You write, "The ion would tend to flow down the conc. gradient
until it is exactly opposed by the charge it is building up. This
equilibrium is what is calculated by the Nernst potential."
The Nernst equations say nothing about the buildup of charge.
What they say is that there is a potential that is indicated by a
difference of concentration across a membrane which acts to reduce
the concentration difference such that ln [K+]outside/[K+] inside will
approach 0 as that ration approaches 1.
You write, "To prove this to yourself [what I am trying to
deny], dig up the free-energy calcs for a charge separation and for a
conc. gradient. Set them equal and opposite to each other.
Bingo, you get the Nernst potential
equations. (textbook: Alberts et al, Mol Bio of the Cell, p 314)
charge: ^G = zFV (^=delta)
conc: ^G = -RTln(Cout/Cin)
so you get zFV = RTln(Cout/Cin)"
Here you are talking about 'free-energy calcs'. Do you know
why they call it free energy? Not because there is so much of it
around to be tapped, but because it can't be tapped. It is the force of
entropy. No one has ever made an apparatus and ever will that runs
on this as a source of energy. There are no perpetual motion
machines! This kind of 'energy' is not like electrical or
electrochemical energy which involves electrons and negative
charge, and which is usable, and which also has the unit 'volts'.
You write, "...to reach the Nernst potential, the ion has
to be permeable. It also would have to be the only ion
involved."
The Nernst equations say nothing about permeability, only ion
concentration gradients. Where does this requirement come from?
The Goldman equation? All that was was a device to explain
experimental results with regard to the effects of K+, Na+, and Cl-
on measured membrane potential in such a way that the results were
those predicted by the Nernst equations. It was believed the
membrane had to be permeable to the select ion otherwise the
Nernst equations wouldn't hold (you couldn't add Ek, Ena, and Ecl and
come up with -65mV, but you could come close is you thought only
Ek was pertinent, =Vm that is). By assuming certain permeabilities
to each of the three ions the Nernst potential could be made to agree
with exprimental results.
You write, "Example: Put two different conc of NaCl across a
membrane. Punch a *NON-SELECTIVE* hole. What happens? Both Na
and Cl flow down conc gradients. Na would try to build a +
charge, Cl a - charge. Result? They cancel."
If this is so, then the Nernst potentials should cancel too
shouldn't they? But they don't. So maybe we're again talking about
two different kinds of potential.
You respond to my : > If these values were
>actually electrical values, then we would have -80mV for the
>resting membrane potential, Vmr.
WITH
"Again, *weighted* average. The ions have to move to build
charge."
I'm not sure what you're talking about here. Do you mean the
ions must collect in a group; certainly not that ionization itself
depends upon movement? If the ions collect in a group, the Nernst
equations address the concentration gradient of two groups, not the
electrical charge of one in relation to another.
You write, "EK and ENa *do* exist simultaneously. And, why
not? They are just the theoretical values for *how much charge
could be separated ***if*** the ion were allowed to move
***and*** it were the only one allowed to move. Open Na
channels, you move towards ENa. Open K channels, you
move towards EK."
But the Nernst equations don't say this. They say that if the
ions are allowed to run across the gradient Ek or Ena goes to zero as
the ratio of ions within and without approaches unity. Ex is
determined by gradients, and the running down of these gradients
doesn't move us toward Ex, instead it runs Ex to 0.
You write, "Why not equate ion gradients with voltage? What's
the difference between separating a charge composed of Cl-
ions and separating a charge composed of electrons? It's still
potential energy, isn't it?"
Here is the problem.
ectrical.
You write, "You're just assuming that there's something
magical about the units of charge that are normally used
for electricity that means that they can't be used to talk
about ionic charge."
It looks like it's the other way around. Tom, it appears that
you and neural science are assuming that there is something magical
that allows Nernst potentials to be equated with electrical
potentials.
You write, "Also, remember that there are (for
historical reasons) a lot of different terms being used. E
and V are identical to the biologist, so don't get screwed
up by that. We measure Vm and Ex now, but if you go back
to original papers, it may be different. (also, the origninal
papers also measured outside voltage wrt inside, thus the signs
were all backwards)"
You then appreciate history and its effects on the formulations
and theorizations and terminology of science. I think neural science
is also a victim of the distorting effect of unarticulated paradigms
or metaphysical views, and that is what we are witnessing here. I
think that all the laboratory tests and measurements taken can be
explained just as well using another approach to the nature of nerve
impulse propagation, to it being semiconduction on an N type
semiconductor, and this is why we have the organic anions of acid
and protein which make up almost as much of a presence in the axon
of the squid as the potassium ions. I think its plain to see that Vm
has nothing to do with ion gradients or the movement of ions, and
this is the central fallacy of modern neural science. I could be
wrong. I'm just a beginner at this, and have yet to complete a course
in it. I am trained in the philosophy and history of science, so I must
profess ignorance.
G.C.O'Kelly
