Abstract

According to the rules of GABAA receptor (GABAAR) subunit assembly, α4 and α6 subunits are considered to be the natural partners of |[delta]| subunits. These GABAARs are a preferred target of low, sobriety-impairing concentrations of ethanol. Here we demonstrate a new naturally occurring GABAAR subunit partnership: |[delta]| subunits of hippocampal interneurons are coexpressed and colocalized with α1 subunits, but not with α4, α6 or any other α subunits. Ethanol potentiates the tonic inhibition mediated by such native α1/|[delta]| GABAARs in wild-type and in α4 subunit–deficient (Gabra4|[minus]|/|[minus]|) mice, but not in |[delta]| subunit–deficient (Gabrd|[minus]|/|[minus]|) mice. We also ruled out any compensatory upregulation of α6 subunits that might have accounted for the ethanol effect in Gabra4|[minus]|/|[minus]| mice. Thus, α1/|[delta]| subunit assemblies represent a new neuronal GABAAR subunit partnership present in hippocampal interneurons, mediate tonic inhibitory currents and are highly sensitive to low concentrations of ethanol.