While GABAA receptor gene variants are believed to modulate the predisposition to alcoholism, the effects of ethanol on GABAA receptor function are not well-understood. The effects of acute ethanol treatment on GABAA receptor function vary widely in vivo and in vitro. A number of reports suggest that low concentrations of ethanol (<5 mM) potentiate GABA responses in some cell types or with specific subunit combinations, notably α4/6 and δ (Borghese and Harris 2007; Sundstrom-Poromaa et al. 2002; Wallner, Hanchar, and Olsen 2003; Wallner, Hanchar, and Olsen 2006). In our study, higher but still pharmacologically relevant concentrations of ethanol (44–100 mM) were required to see effects with “less-sensitive” GABAA subunit combinations. Acute ethanol treatment significantly potentiated GABA induced currents in cells injected with a 1:1:1 and 2:2:1 ratios of human α2β2γ3 subunits, whereas ethanol inhibited GABA responses in cells injected with a 6:2:1 ratio. Our results are notable for two reasons as we describe significant ethanol potentiation in GABAA receptors lacking α4/6 and/or δ subunits and we observed potentiation or inhibition by ethanol which was dependent on subunit ratio. The specificity
