Anaesthetic concentrations of alcohols potentiate GABAA receptor-mediated currents: lack of subunit specificity.
Anaesthetic concentrations of ethanol (50-400 mM) and butanol (1-20 mM) were tested for their effects on GABAA receptor-mediated chloride currents in Xenopus oocytes expressing human GABAA receptor cDNAs. Significant potentiation of the currents was seen in all receptor constructs tested. Substituting the alpha 5 subunit for the alpha 1, or the beta 2 for the beta 1, did not affect the degree of ethanol potentiation. The effects of 200 mM ethanol and 20 mM butanol were also tested using a variety of GABA concentrations (0.3-1000 microM) on oocytes expressing alpha 1 beta 1 vs. alpha 1 beta 1 gamma 2S or alpha 1 beta 2 vs. alpha 1 beta 2 gamma 2S receptor constructs. The presence of the gamma 2S subunit generally did not appear to affect the degree of potentiation, except that butanol potentiation was greater in alpha 1 beta 1 than in alpha 1 beta 1 gamma 2S receptors. This phenomenon of anaesthetic concentrations of alcohols potentiating GABAA receptor responses appears to be distinct from the low (20 mM) ethanol potentiation previously reported in the literature.
Mihic
S J
SJ
Department of Pharmacology, University of Colorado Health Sciences, Center, Denver 80262.
Whiting
P J
PJ
Harris
R A
RA
D020001:1-Butanol; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000440:Butanols / Q000494:pharmacology*; D018118:Chloride Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D009865:Oocytes / Q000378:metabolism; D011963:Receptors, GABA-A / Q000502:physiology*; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000777:Anesthetics; D000440:Butanols; D018118:Chloride Channels; D011963:Receptors, GABA-A; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D020001:1-Butanol