Hyperpolarization of Neurons

Richard Burge R.Burge at bay.cc.kcl.ac.uk
Fri Apr 29 11:35:58 EST 1994

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

>       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?

These agents (barbiturates, sedatives, etc) modulate the activity of the 
GABA-A receptor (sorry - I can't do subscripts in plain ASCII), such that it 
is easier to open it's intrinsic chloride channel and hyperpolarize the 
neuron. Activity - motor activity, concious thought, whatever - requires 
neuronal transmission in the form of action potentials, and these are induced 
by depolarizing a neuron past it's threshold potential. If you hyperpolarize a 
neuron, as inhibitory GABAergic inputs do, the membrane potential has further 
to go to reach threshold and fire an action potential.

In short, if you enhance inhibition of neuronal firing by using barbiturates 
or whatever, the nervous system becomes less active. There is a high level of 
inhibition of neuronal activity in the resting state, so the nervous system 
constantly has a brake on it. Consequently, if you remove inhibition, using 
GABA-A agonists for example, you get overactivity. This is why pumping 
yourself full of Strychnine (a glycine receptor agonist - glycine is another 
inhibitory transmitter) or have Huntingdon's Chorea, in which GABAergic 
transmission is compromised, you twitch, have hyperkinesia, etc.

Incidentally, there are some situations in which GABA depolarizes neurons. In 
many developing neurons, for example, the chloride potential is such that 
opening chloride channels results in an _efflux_ of chloride, depolarizing the 
cell. GABA can thus act as an _excitatory_ transmitter!

You should read up on the basic theory behind neuronal transmission, action 
potentials, ion channels, that sort of thing - have a look in any basic 
physiology textbook.

Richard Burge         | e-mail:
King's College London |  R.Burge at bay.cc.kcl.ac.uk

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