Low doses of ethanol and a neuroactive steroid positively interact to modulate rat GABA(A) receptor function.
Fast inhibitory responses in the central nervous system are mediated by the GABA(A) receptor. The activation and function of the GABA(A) receptor can be modulated by a variety of compounds including benzodiazepines, barbiturates and neuroactive steroids. Modulation of the GABA(A) receptor function by ethanol has been observed in some but not all studies. We have studied the effect of ethanol at concentrations corresponding to light intoxication on the function of the recombinant GABA(A) receptor containing alpha1beta2gamma2 subunits. The experiments were performed both in the absence and presence of low, subthreshold concentrations of a neuroactive steroid. The results demonstrate that, in the presence of the steroid, 0.05 % (9 mM) ethanol potentiates the GABA(A) receptor function by increasing the channel mean open duration. No effect was observed on the channel closed time durations. The data suggest that ethanol influences channel closing with no effect on the affinity of the receptor for GABA or the channel opening rate constant.
Akk
Gustav
G
Department of Anesthesiology, Washington University School of Medicine, Campus Box 8054, 660 S. Euclid Avenue, St Louis, MO 63110, USA. akk@morpheus.wustl.edu
Steinbach
Joe Henry
JH
D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
D000732:Androstanols; D007473:Ion Channels; D009570:Nitriles; D011963:Receptors, GABA-A; D000431:Ethanol; C084682:3-hydroxy-5-androstane-17-carbonitrile; D005680:gamma-Aminobutyric Acid