ANESTHETIC CONCENTRATIONS OF ALCOHOLS POTENTIATE GABA(A) 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 GABA(A) receptor-mediated chloride currents in Xenopus oocytes expressing human GABA(A) 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 mu M) 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 2(S) receptors. This phenomenon of anaesthetic concentrations of alcohols potentiating GABA(A) receptor responses appears to be distinct from the low (20 mM) ethanol potentiation previously reported in the literature.