The mitochondrion as a flip-flop memory element in neurons

Andrew Gyles syzygium at alphalink.com.au
Sun Dec 10 22:52:16 EST 2000




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.

Low mtDNA mutation rate in humans?

This article, like the earlier one ('Mitochondria as the motors of
consciousness'), is speculative. The validity of both models will
depend on a detailed examination of the magnitudes of the various
physical quantities involved. If the models are valid they will support
the notion that the mutation rate in the mtDNA of humans might be very
much lower than that in apes, for reasons I outlined in the earlier
article.

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.

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.

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'.

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.

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.

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.

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.

Andrew Gyles

http://www.geocities.com/acgyles


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