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neuron energy use

steve madison s.madison at sympatico.ca
Sun Oct 25 17:51:24 EST 1998


Hi gang,

sorry ken, couldn't understand anything you were trying to get at in your reply
but i thought jimmy had some pretty interesting (if not very easy to answer)
questions:

jimmyd at cc.gatech.edu wrote:

> I want to know a few things about Neuron energy use.
> Please email me any ansewrs!  Thanks in advance.
>
> * Neurons get all their energy from glucose, right? (Kolb & Whishaw 1996, p
> 68)
>

Yes they do, under normal circumstances.  Most of the questions you pose are
actually biochemical in nature (and unfortunately i'm not a trained biochemist but
have come across these types of questions in work on muscle nerves).  My biochem
text is in the lab, but I seem to recall that if glucose is in short supply
(starvation, uncontrolled diabetes) the brain can make do with alternate fuel
(fats).  Unfortunately this results in the production of ketone bodies leading to
ketoacidosis (a condition showing mental confusion, dyspnea, nausea, dehydration,
and if untreated, coma [Mosby's Medical Dictionary]).

> * The mitochondria turns glucose into ATP. Does the cell body have a storage
> of ATP, or does the mitochondria produce it as needed?
>

There is a limited supply of ATP in the body (typical concentration of 3-8 mM ATP)
and must be continuously produced.  But not all ATP is produced in the
mitochondria.  Under limiting conditions of oxygen you can produce ATP in the
cytosol (substrate level phosphorylation).

> * How much glucose (turned into ATP) is needed to fire a neuron? If the firing
> rate of a neuron is 700 per second, what is the rate of glucose use?
>

According to Principles of Neural Science, "...the metabolic rate for glucose
ranges from approimately 7 mg/100g/min in the parietal corte to 10 mg/100g/min in
the visual cortex; the subcortical white matter has a rate of approximately 4
mg/100g/min."  I would assume this is for normal, resting conditions and during
specific tasks that would utilize those brain regions.  Anyone care to clarify
this?  As for calculating the amount of ATP used in a single neuron firing at 700
Hz.... That I can't help you with.  However, I seem to recall a paper by
Wong-Rielly (Nature, 1984; 307:262-264) in which she breaks down the percentages
of metabolic use in a neuron.  So much to maintain membrane potential, for
synaptic processes, or some such.  Sorry I can't add more to this.  It has brought
to mind the idea of "metabolic cost".  That is, is it less metabolically costly to
maintain cell constituents (membrane, synaptic contacts, dendrites, proteins or
neurotransmitters) or use the ATP to generate (used in ribosomes and DNA->RNA
production) new proteins on the fly?  Do you renovate, or tear it down and build
new?

> * If neurons get all their energy from glucose, then what is the purpose of
> oxygen in the brain?
>

Oxygen is vital to oxidative phosphorylation in the mitochondria.  It is the final
electron acceptor that powers the movement of hydrogen across the inner
mitochondrial membrane.  Perhaps I should step back a bit.  The following process
can be read in any fundamental biochemistry text (e.g., Biochemistry, Voet and
Voet).  Glucose enters the cell (facillitated transport, usually the GLUT family
of receptors) where it is metabolised to pyruvate.  Pyruvate is transported into
the mitochondrion, converted to Acetyl-CoA and follows the citric acid cycle
(a.k.a. the krebs cycle, or the tricarboxylic acid cycle), transfering electrons
to reducing agents (NAD+ and FAD) along the way.  These reducing agents are passed
on through the electron transport chain where they are re-oxidized and oxygen is
the final acceptor of electrons in this process.  The electron transport chain
pumps H+ across the inner mitochondrial membrane.  As these protons return across
the membrane along their concentration gradient, it is through an ATP synthase
complex that produces ATP from ADP and Pi.  Without oxygen the electron transport
chain does not work and ATP is not produced (remember that some ATP can still be
made in the cytosol).That was about 200 pages of biochem in a paragraph.  Meaning
that most (if not all) is very simplified, if not containing outright errors.  I
suggest you pull out a biochemistry textbook.

> * This is my conception: The dendrites send a message to the soma indicating
> the change of firing rate. The soma takes energy from the bloodstream to
> raise the firing rate. This message is in the form of the chemical state
> inside the dendrites and soma. What is wrong with this conception?
>

This is a big one.  Principles of Neural Science (and probably others) handle it
nicely.  Generally, the dendrites change their membrane potential due to the
binding of neurotransmitters to receptors that influence ion channels.  As ions
flow in or out, the membrane potential alters.  All of these minor alterations in
membrane potential are compiled (summation) and if a threshold value is reached,
the neuron will instigate an action potential.  This is the conversion of a
chemical signal (neurotransmitters) to an electircal signal (membrane potential).
The more often you reach the threshold value, the more often the neuron will
fire.  It takes energy (ATP) to return the membrane to its resting potential.

> The following questions assume the above conception is correct.
> * What happens if a neuron is heavily stimulated with messages from its
> dendrites, but there is not enough energy in the local bloodstream to increase
> the firing rate very much?
>

Happens all the time.  They are called refractory periods in which a neuron cannot
fire again.  But I think you mean what happens in the case of a lack of energy.
Not much as long as it is temporary.  The neuron just becomes inoperable for a
while, or fatigues if we are talking about muscle cells.  If someone is choking
you (not enough oxygen to the brain = not enough ATP being produced) you will
"black out" or faint.  Although this IS damaging to the brain, you do recover.
You can also experience a similar effect by rubbing the eyes.  It takes a second
or two for sight to return.

> * What happens to the message after the rate changes (or doesn't in the case
> of low energy)?
>

The "message" or action potential has already been sent down the axon usually
before the neuron fatigues.  Or if we take the case of "blacking out", the message
is lost.

Hope this was of some help.

> Thanks!
>
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Steve Madison
Neuromuscular Research
Laurentian University
Sudbury, Ont.
Cananda




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