Hyperpolarization of Neurons

Charles E. Weaver wheat at mbcrr.harvard.edu
Tue Apr 26 05:38:33 EST 1994

In article <1994Apr25.134819.1864 at debug.cuc.ab.ca>, Mdh at debug.cuc.ab.ca
(Mike Hamilton) wrote:

> 	I am curious, I have been reading about the GABA inhibitory 
> neurotransmitter, and how the sedatives such as alcohol and barbiturates 
> are attributed to their actions on these receptors. The reasoning behind 
> it is that a barbiturate would attach to the receptor would would result 
> in the opening of a chloride channel, which in turn results in the 
> hyperpolarization of the neuro and thus sedation? Could someone explain 
> why this hyperpolarization of the neuro would result in sedation? From 
> what I understand, the average potential across a neuron is approx. 90mV, 
> so why would increasing this sedate a person?
> 	Thanks
> 		Mike

   As I'm sure you know cell to cell communication in the CNS involves the
propogation of action potentials (a wave of depolarization moving through
individual neurons), that are initiated when inputs in the form of
neurotransmitter triggered openings of ion channels depolarize the cell to
the threashold potentail (-30 mV would be a good guess).  Everything that
you say about GABA is pretty much correct, but the normal resting potential
for neurons is more like -60 mV (I don't know if you meant -90 in your
post, but all living cells have negative resting potentials due to the
electrogneic nature of the Na/K pump).  The reason that hyperpolarization
is inhibitory is simply that a cell that is hyperpolarized is farther away
from the threashold potential for firing an action potential.  As to why
sedation results.....conciousness is generally considered to involve
neuronal transmittion through a structure in the brain called the reticular
formation, that consists of long strings of neurons.  If activity is
decreased in these neurons the result is sedation.  There is a statistical
argument for why these neurons are effected before other sets of neurons in
the brain that consist of shorter chains of neurons.  Simply stated in a
chain of neurons it only takes inhibition of one neuron to inhibit the
whole chain, therefore longer chains of neurons are more likely to be
effected than shorter chains because the target is bigger.  This argument
also holds for general anesthetics ability to effect sedation.

   To really understand what hyperpolarization is you should read up on the
electrophysiology of neurons.  A good source is Principles of Neural
Science by Kandell, Shwartz, and Jessell  Parts II and III contain lots of
basic stuff.

Good luck,


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\\^//   Charles E.Weaver
\\^//   Boston University School of Medicine    Phone (617)638-5323
  |     Department of Pharmacology L-603        Fax   (617)638-4329
  |     80 East Concord Street Boston MA 02118  cweaver at acs.bu.edu

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