|MadSci Network: Biochemistry|
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, Terry
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