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.