The mitochondrion as a flip-flop memory element in neurons

Andrew Gyles syzygium at alphalink.com.au
Mon Dec 11 18:21:40 EST 2000


In article <913alq$2ub$1 at mercury.hgmp.mrc.ac.uk>,
  Rich Cooper <richcooper1 at mindspring.com> wrote:

> > 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.
>
> Are you sure that a single proton generates enough charge transfer
> to start the avalanche of ion exchange that produces the nerve
impulse?
> This question should be answerable by a simulation.  My own feeling
> is that one proton is probably not adequate to start the avalanche.

I think that many protons would arrive at the inside of the membrane of
the neuron to trigger a nerve impulse. There might be millions of
identical ATPase enzymes rotating in phase, advancing in big steps of
120 degrees, and each pumping uphill 4 protons at each big step. That
is why I wrote of a 'minor flood' of protons being produced at each big
step.
>
> > Triggering of 'gamma' waves
> >
> > I have suggested that a mitochondrion close to a 'critical spot' on
the
> > inner surface of the membrane of a neuron might work sometimes with
its
> > ATPsynthase/ATPase enzymes rotating in phase as ATPase, fuelled by a
> > store of ATP in the matrix of the mitochondrion, and triggering
nerve
> > impulses in the neuron at three times the frequency of rotation of
the
> > ATPase enzymes.
> >
> > I proposed that this might be the origin of the 'gamma' waves
observed
> > in certain groups of neurons. These waves have been tentatively
> > identified by some authors as the neural correlate of 'awareness'
> > or 'consciousness' of particular aspects of objects.
>
> Since there is no way to measure 'consciousness' or 'awareness', I
find
> any neural correlates to be extreme speculation, rather than any
hypothesis
> that can be scientifically built upon.

'Consciousness' and 'awareness' are difficult to define. Every person
might have their own definitions! Nonetheless several workers,
including Francis Crick and Christof Koch, have tried to study
consciousness experimentally. Crick and Koch studied awareness in the
visual system.
>
> > I suggested that the triggering of such waves by a mitochondrion
might
> > continue until the mitochondrion exhausted its store of ATP, when
its
> > rotating enzymes would have to reverse their direction of rotation
and
> > work as ATPsynthase, making ATP and storing it in the matrix (the
inner
> > hollow) of the mitochondrion. This reversing of mode of operation,
from
> > ATPase to ATPsynthase, and then back to ATPase and so on would, I
> > suggested, produce the 'rhythmic' character of the 'gamma' waves
that
> > some researchers have observed.
>
> The three phase rotation provides some very useful material for
> developing experimental conditions that might shed more light on the
> mechanisms of mtDNA involvement in nerve cells.  Perhaps you
> can state a hypothesis that could be experimentally validated or
> contradicted.  Such a hypothesis could become very useful to the
> field whether it is eventually proven or disproven.
>
> > A more interesting mode of operation
> >
> > I now propose that a mitochondrion in a particular situation inside
a
> > neuron, with one of its sides pressed close to the inside of the
> > membrane of the neuron, might operate in a more complex manner, and
one
> > more interesting to those workers trying to find parallels between
the
> > operation of a computer and the operation of the brain.
> >
> > I shall call the side of the mitochondrion pressed close to the
inside
> > of the membrane of the neuron the 'near' side, and the opposite
side of
> > the mitochondrion the 'far' side. I suggest that the contact between
> > mitochondrion and neuron might be rather like the contact of two
> > neurons at a synapse, except of course that the mitochondrion is
inside
> > the neuron (not outside it), and is smaller than a typical synapse.
> >
> > There are cristae on the 'near' side of the mitochondrion and
cristae
> > on the 'far' side. These are infoldings of the inner membrane of the
> > mitochondrion. Identical ATPsynthase/ATPase enzymes are inserted in
> > these cristae, close to each other (I assume) in a regular
arrangement
> > a bit like the molecules in a single layer of the lattice of a
crystal.
> > There may be millions of these identical enzymes, rotating like
motors
> > in phase, in the cristae of a single mitochondrion.
> >
> > Near side has two stable states
> >
> > I propose that in particular mitochondria performing information
> > storing and processing tasks in particular parts of a neuron the
> > ATPsynthase/ATPase enzymes in the cristae on the 'far' side work
always
> > as ATPsynthase.
> >
> > And I propose that the ATPsynthase/ATPase enzymes in the cristae on
> > the 'near' side work sometimes in phase as ATPsynthase and
sometimes in
> > phase in reverse as ATPase, in the latter case producing 'minor
floods'
> > of protons at three times the frequency of rotation of the central
> > asymmetric 'axle' of the enzyme. From now on I shall refer to
> > these 'minor floods' of protons as 'waves'.
>
> Protons would unbalance the electrostatic signals of the
mitochondrion, and
> might also rotate it, so that the near side becomes the far side, or
just
> rolls
> it 120 degrees.  The near side must have some force that makes it take
> the near side, or vice versa with the far side, so that movement of
charges
> can cause rotation of the mitochondrion.

In my models it is the reversible ATPsynthase/ATPase enzymes that
rotate synchronously and in phase. They are very much smaller than the
mitochondrion, which is roughly as big as a bacterium. I do not think
that the mitochondrion rotates.
>
> > Switchable if volley phase is right
> >
> > If a volley of impulses passed through the neuron with the same
> > frequency and phase as the waves of protons being produced on the
near
> > side of a mitochondrion with its enzymes working as ATPase the near
> > side would 'see' high concentrations of positive charge at the
peaks of
> > the waves, and would (I propose) be 'pushed' into reverse by these
high
> > concentrations so that it worked as ATPsynthase and produced no
waves
> > of protons.
> >
> > I say 'pushed' because the positive charges appearing on the inside
of
> > the membrane of the neuron would repel the protons being produced by
> > the near side of the mitochondrion. (A nerve impulse consists of a
> > patch of positive charge appearing to travel along the inside of the
> > membrane of the neuron in the direction of the impulse. After it has
> > passed, the charge on the inside of the membrane becomes negative.)
> >
> > If a volley of impulses passed through a neuron with the same
frequency
> > as, but opposite phase to, the waves of ATP being produced on the
near
> > side of a mitochondrion with its enymes working as ATPsynthase the
near
> > side would 'see' high concentrations of negative charge at the
peaks of
> > the waves of ATP and would be 'pulled' into reverse so that its
enzymes
> > worked as ATPase and produced waves of protons.
> >
> > I say 'pulled' because the negative charges appearing on the inside
of
> > the membrane of the neuron would attract any protons in the near
side
> > of the mitochondrion and by drawing them outside it lower the
> > concentrations of protons inside the mitochondrion.
> >
> > Switchable memory element
> >
> > The reader will, I think, immediately see the significance of the
above
> > two changes. In the first case the mode of operation of the enzymes
in
> > the near side of the mitochondrion is switched from a mode producing
> > waves of positive charges to a mode producing no positive charges.
In
> > the second case the mode of operation is switched from one
producing no
> > waves of positive charges to one producing waves of positive
charges.
> >
> > Unswitchable if phase is wrong
> >
> > If a volley of impulses passed through the neuron with the same
> > frequency as, but opposite phase to, the waves of protons being
> > produced on the near side of a mitochondrion with its enzymes
working
> > as ATPase the near side would 'see' low concentrations of protons
> > (because the inside the of the neuron near the mitochondrion would
be
> > negative when each wave of protons reached its peak) and would
> > therefore continue to work as ATPase.
> >
> > If a volley of impulses passed through a neuron with the same
frequency
> > and phase as the waves of ATP being produced on the near side of a
> > mitochondrion with its enzymes working as ATPsynthase the near side
> > would 'see' high concentrations of positive charge at the peaks of
the
> > waves of ATP and its enzymes would continue to work as ATPsynthase.
> >
> > The mitochondrion as a flip-flop
> >
> > In the four cases described above the near side of the mitochondrion
> > can be seen as analogous to a 'flip-flop', a circuit defined in
United
> > States usage as 'a bistable pair of valves or transistors, two
stable
> > states being switched by pulses ... '.
> >
> > I do not push this analogy too far. Perhaps it would be better to
> > regard such a mitochondrion as simply a binary cell, defined as 'An
> > information storage element, which can have one or other of two
stable
> > states'. However, its current state does not have to be discovered:
it
> > is continually communicated by the mitochondrion itself.
>
> If a mitochondrion has two (or three) stable states, that is
sufficient
> to exhibit a kind of memory based on neural impulses terminating at
> the neuron.  The short term memory effect might be experimentally
> validated, or simulated, by such a mechanism.  Whether there are
> two or three states is unimportant to establish the value of this
> line of theory.
>
> > The near side of the mitochondrion has two stable states: enzymes
> > working as ATPase or as ATPsynthase. It can be switched between
these
> > states by volleys of nerve impulses of particular frequency and
phases,
> > but not by volleys of the 'wrong' phase relative to the current
stable
> > state.
> >
> > Active memory
> >
> > The near side of the mitochondrion can be seen as an active memory
> > store, in the sense that in one of its two modes of operation it
> > continually triggers nerve impulses, which can be communicated to
other
> > neurons, and in the other mode it triggers no nerve impulses. In the
> > appropriate context the lack of an impulse is a signal too.
> >
> > Thus it is not a passive memory store, like the patches of differing
> > magnetic polarity on the surface of a computer hard drive, whose
state
> > has to be discovered by an actively interrogating reading head.
>
> It sounds more like a gate-memory combination where in one state, it
> conducts or repeats impulses from input to output, and in another
state,
> it terminates impulses using an electrical damping network.
>
> > Short-term memory
> >
> > I propose that mitochondria working as described above could be the
> > basis of short-term memory.
> >
> > Binary arithmetic
> >
> > I propose that several, perhaps many, such mitochondria in the one
> > neuron might enable it to do binary arithmetic and to process
> > information. Perhaps it is relevant to note here that some neurons
have
> > many dendritic branches, and that a nerve impulse can travel in both
> > directions along the membrane of a neuron.
>
> Some sort of accumulation of impulses is needed to explain the long
> term memory (possibly synapse conditioning), but binary arithmetic
> seems a bit far to speculate.  I doubt if it exists in the brain,
because
> people mostly don't naturally know math without being trained a lot.
>
> > Frequency detectors
> >
> > A switching volley of nerve impulses must have a frequency three
times
> > the frequency of rotation of the enzymes in the near side of the
> > mitochondrion. If each mitochondrion ran at its own frequency of
> > rotation (governed, for example, by the supply and removal of
> > metabolites in a particular situation) it could be switched only by
a
> > volley of nerve impulses of three times that frequency.
> >
> > Thus incoming volleys could switch different mitochondria in the one
> > neuron, depending on the frequency of each volley.
>
> This could explain mechanisms in the cochlea that respond to
frequencies
> of sound in bands of cochlear nerves.  Again, some simulation of the
> hypothesized processes might show a clear mechanism related to the
> mitochondrion.
>
> > Andrew Gyles
> >
> > http://www.geocities.com/acgyles
>
> -Rich
>
>

Thank you for your comments.

Andrew Gyles

http://www.geocities.com/acgyles


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