MadSci Network: Biochemistry

Re: How does alcohol actually promote the working of GABA receptors?

Date: Wed Mar 15 13:47:25 2000
Posted By: Terry Hebert, Faculty, Universite de Montreal, Biochemistry, Montréal Heart Institute
Area of science: Biochemistry
ID: 953076320.Bc

Dear Jason,
	That's an interesting question. Alcohol and GABA actually potentiate 
each others actions. That is to say, they somehow interact such that lower 
concentrations are required to achieve the same effects. That's why doctors 
always tell you not to drink alcohol if you're taking barbituates- i.e. it 
is very dangerous. For one class of GABA receptors, GABA-A, which belong to 
a class of proteins called ligand-gated ion channels, alcohol enhances the 
current flowing through these channels in response to the binding of GABA. 
These receptors when activated hyperpolarize neurons, rendering them less 
excitable- i.e. GABA receptors are inhibitory. Alcohol, makes these 
receptors even more inhibitory leading to a generalized sedative effect. 
Your question relates to the mechanism of alcohol action on GABA receptors. 
Well, we do know that alcohol doesn't change the size of the current 
flowing through a single GABA-A channel. However, it does increase the 
frequency of opening and the time spent open. At the molecular level, we 
still don't know exactly what's going on. GABA-A receptors belong to class 
of proteins which are imbedded in the cell membrane. We do know that 
alcohol (which is hydrophobic) can get into the membrane. We also know from 
molecular biological studies of different GABA-A receptor subtypes, that 
the 2nd and 3rd transmembrane domains (these receptors have 5 subunits with 
4 transmembrane domains each, see figure) are important for the effect of 
alcohol on receptor function. Perhaps, alcohol binds the receptor in or 
near these domains and causes alterations that lead to the increased time 
spent in the open state.
Hope this helps,


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