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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