The mitochondrion as a flip-flop memory element in neurons

Richard Norman rsnorman at mediaone.net
Tue Dec 12 20:17:24 EST 2000

"Andrew Gyles" <syzygium at alphalink.com.au> wrote in message
news:916g5k$dl3$1 at nnrp1.deja.com...
> In article <J3rZ5.16970$Uj7.546529 at typhoon.mw.mediaone.net>,
>   "Richard Norman" <rsnorman at mediaone.net> wrote:
> > "Andrew Gyles" <acgyles at my-deja.com> wrote in message
> > news:913oq4$6on$1 at nnrp1.deja.com...
> > >
> > >
> > > (Related articles at: http://www.geocities.com/acgyles)
> > >
> > > The mitochondrion as a flip-flop memory element in neurons
> > >
> > > I suggested in an earlier article that if certain mitochondria in
> > > neurons worked with all of their ATPsynthase/ATPase enzymes
> rotating in
> > > phase or [to allow for geometric effects at the bends of cristae] in
> > > phase plus or minus 120 degrees, they would produce 'minor floods'
> of
> > > protons when working as ATPsynthase, which could trigger nerve
> impulses.
> > >
> > > Protons are positively charged. The arrival of positive charges at
> the
> > > negatively charged inner surface of a neuron membrane that is ready
> > > to 'fire' will trigger a nerve impulse. The triggering positive
> charge
> > > need only be very small; the main strength of a nerve impulse is
> > > contributed by the subsequent increase in permeability of the
> membrane
> > > to sodium ions, and the inrush of that ion into the neuron.
> >
> > <snip a lot of stuff>
> >
> > I have not noticed in electron micrographs any particular
> concentration
> > of mitochondria right under the cell membrane especially at the site
> > of spike initiation.  Have you tried calculating the actual number of
> > protons that would be required to depolarize a neuron by even a few
> > mv for a reasonable time (at least a significant fraction of a time
> > constant)
> > over a substantial distance (at least a significant fraction of a
> space
> > constant) and allowing for diffusion in the bulk intracellular medium?
> > Then have you tried calculating the effect on the intracellular pH?
> >
> > I would guess that you will kill all the proteins in the vicinity
> with all
> > those protons.  These are not inert charge carriers like K+ or Na+.
> > They are exceptionally active!
> >
> >
> Thank you for your comments. I have not calculated how many protons
> would be required to trigger a nerve impulse. But I suggest that a
> mitochondrion would be capable of pumping out many protons in
> each 'minor flood' or 'wave'. There might be millions of identical
> ATPase enzymes rotating in phase in a single mitochondrion.
> Would it be true to say that the smaller the diameter of the part of
> the nerve concerned the fewer the protons required to trigger an
> impulse?
> Is it possible that protons would have a more powerful triggering
> effect (in relation to their number) than other positive ions? And that
> fewer of them would be required because of this?
> I am aware that the proton is the active part of acids (I assume that
> in the cell it is in the form of the hydronium ion), and I am concerned
> about its potentially destructive effects. However, all mitochondria
> produce protons when their ATPsynthase/ATPase enzymes are working 'in
> reverse'as ATPase. The protons are pumped to the outside of the inner
> membrane of the mitochondrion; the outer membrane is permeable to ions,
> I understand. So I assume that the bulk intracellular medium is
> sufficiently well buffered to prevent a big fall in pH. It is also
> possible that most of the protons are 'tethered' to the inner membrane
> by the attraction of negative ions in the matrix of the mitochondrion.
> (There is a sodium ATPsynthase/ATPase in a bacterium, which pumps out
> sodium ions when it is running 'in reverse' as an ATPase. It is thought
> to be very similar in its rotary mode of operation to the proton
> ATPsynthase/ATPase in eukaryotes.)
> I suggested that the mitochondrion might have one side close to the
> inside of the membrane of the neuron. That would reduce diffusion into
> the bulk intracellular medium. If no mitochondria are observed close to
> the membrane of neurons in places where an impulse could be triggered
> my hypothesis would seem unlikely to be correct. Have you seen any in
> the dendrites?
> Andrew Gyles
> http://www.geocities.com/acgyles
I am not an anatomist and don't know the details of where mitochondria
are located.  But if there were a particular association with a specific
site in the neuron, it would likely be noted.

You really have to work out the stoichiometry of just how many protons
are really likely to be involved in any particular reaction.  And also
consider that the production of protons must also necessarily involve
the production of an equal number of anions that are hanging around

The bigger problem with the hypothesis is convincing anyone that it
really can be found in any particular cell.  Experimental neurobiologists
are not particularly interested in theoretical calculations that this or
that might happen.  They want to know what actually does happen
in particular cells in particular instances.  There are abundant cellular
activities that influence membrane potential.  For example, the
electrogenic sodium pump in fact generates a transmembrane
current that varies with time.  But try to find an example of a cell
that uses such a thing for signaling or information processing!

In earlier days of electophysiology, people were always suggesting
hypotheses like electron tunneling across the membrane or protein
fixed charge movements producing nerve potentials.  However, the
classic "ionic theory" is the only thing that has withstood the test
of time.  So, yes, all kinds of intracellular signaling pathways can
modulate the excitability of membrane channels.  But that just
says the nervous system is complicated.  The real question is to
find out exactly which pathways modulate the excitability in
exactly what way under exactly what conditions.  So you are going
to have to provide some experimental tests to get people

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