Recent studies suggest that EtOH potentiation of GABAA receptor function depends on protein phosphorylation. Messing and co-workers have shown that activity of the epsilon subunit of protein kinase C (PKC) is necessary for EtOH potentiation of γ2-subunit-containing GABAA receptors expressed heterologously in a mammalian cell line (Qi et al. 2007). This PKC action appears to involve phosphorylation of a specific serine residue on the γ2 subunit. This finding may explain data from previous studies indicating the involvement of PKC in EtOH potentiation of GABAergic transmission (Weiner et al. 1994). However, in this earlier study it was not clear if the EtOH effects on transmission involved pre or postsynaptic mechanisms. A parallel line of investigation indicates that PKCδ is necessary for EtOH potentiation of tonic current involving δ-subunit-containing GABAARs (Choi et al. 2008). It is not yet clear whether acute EtOH exposure activates PKC phosphorylation of the GABAAR or whether phosphorylation on key amino acid residues is permissive for EtOH potentiation of receptor function, and this will be an interesting topic for future research.
