Trafficking of GABAA receptors can be regulated by many protein kinases, including PKC. Chronic ethanol consumption decreases association of PKCγ with α1-GABAA receptors and decreases expression of the α1 subunit at the cell surface. In contrast, chronic ethanol exposure increases association of PKCγ with α4-GABAA receptors and increases expression of α4 at the cell surface (Kumar et al. 2002). However, in the hippocampus, the association of PKCγ with GABAA receptors is not altered and there is no alteration of α1 subunit expression following chronic ethanol exposure (Kumar et al 2004). Therefore, it appears that association of PKCγ with GABAA receptors and phosphorylation of subunits may influence the trafficking of receptors in vivo following chronic ethanol administration. The increased association of PKCγ with α4-GABAA receptors may phosphorylate GABAA receptor subunits and prevent recognition of the receptor by AP-2, thus preventing its internalization. Indeed, it has been shown that phosphorylation of GABAA receptor subunits reduces the binding of receptors with AP-2 and subsequent internalization (Kittler et al. 2005, 2008). In addition, reduced PKC-dependent GABAA receptor phosphorylation enhances receptor binding to the AP-2
