The mitochondrion as a flip-flop memory element in neurons

Andrew Gyles syzygium at alphalink.com.au
Wed Dec 13 15:39:11 EST 2000


In article <E6AZ5.405$M45.30143 at typhoon.mw.mediaone.net>,
  "Richard Norman" <rsnorman at mediaone.net> wrote:
> "Andrew Gyles" <syzygium at alphalink.com.au> wrote in message
> news:916g5k$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
> somewhere.

That is true. In the case of the neuron membrane the positive ions are
pumped to one side and the anions are kept on the other (though there
is a continuous 'leakage' across the membrane).

In the case of the mitochondrion inner membrane the same thing happens.
ATPsynthase is driven by a continuous supply of protons from the
outside, which drive the rotating 'motor'. There must be anions,
presumably mainly hydroxyl ions, on the inside. The protons combine
with hydroxl to give water.

I suggest that if a mitochondrion with its enzymes running as ATPase is
close to the neuron membrane 'waves' of protons can cross from the
former to the latter.

>
> 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.

With all due respect, an idea has to start as a mere idea. And the
stakes are high: the prospect of a real organelle, about which much is
known already, acting in some situations as a 'flip-flop' memory
element in a neuron. I shall certainly do my best to think of
experiments to test the hypothesis. At this stage I can only hope that
workers in various specialist fields of neuroscience become aware of
the hypothesis and perhaps contribute observations that might support
or disprove it.


  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
> interested.
>
>

Thank you for your comments, which I have found helpful and thought-
provoking.

Andrew Gyles

http://www.geocities.com/acgyles


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