Selective effects of alcohols on γ-aminobutyric acid A receptor subunits expressed in human embryonic kidney cells

Several previous studies implicated α₆ and γ(2L) subunits as potential determinants of γ-aminobutyric acid A (GABA(A)) receptor channel sensitivity to alcohol modulation. The effects of ethanol and n-octanol were studied on GABA-induced currents in human embryonic kidney cells transfected to express one of three different GABA(A) receptor channel subunit combinations: α₁β₂γ(2S), α₆β₂γ(2S) or α₀β₂γ(2L). No increase in the current amplitude of any subunit combination was observed after the coapplication of GABA and physiological concentrations (10-100 mM) of ethanol. By contrast, the coapplication of GABA and 100 μM octanol increased the current amplitude by 50% to 100% in all three subunit combinations. Octanol produced a shift of the current dose-response curve toward lower concentrations of GABA. Ethanol was effective in increasing the rate of desensitization produced by higher concentrations of GABA in the α₆β₂γ(2S) cells but not the α₁β₂γ(2S) combination. This ethanol-induced modification of desensitization was not altered by the presence of the protein kinase inhibitor 1-(5- isoquinolinesulfonyl)-2-methylpiperazine (H-7). These experiments indicate that the presence of α₆ or γ(2L) subunits, in itself, does not result in the potentiation of GABA-induced currents by ethanol, as described in some reports. However, the presence of either the α₆ or α₁ subunit may determine whether the desensitization rate of the GABA(A) current is affected by the alcohol.