A large volume of recent work has focused on the role of PKC as a regulator of GABAA receptor function following ethanol exposure. Various PKC isoforms associate with GABAA receptors and therefore may alter receptor subunit phosphorylation and function. PKCβ associates with GABAA receptor β subunit and alters GABAA receptor phosphorylation and function (Connolly et al. 1999). PKCγ co-immunoprecipitates with α1- and α4-GABAA receptors in the cerebral cortex (Kumar et al. 2002) and PKCε co-localizes with various GABAA receptor subunits across the brain (Olive and Hodge 2000). Similarly, PKCδ alters the function of extrasynaptic GABAA receptors (Choi et al. 2008). Despite the existence of several isoforms of PKC, genetic deletion of PKCγ, PKCε, and PKCδ has clearly demonstrated that these isoforms are major players in ethanol-mediated modulation of GABAA receptor function both in vitro and in vivo. For example, PKCγ knockout mice show reduced sensitivity to the anxiolytic effects of both intoxicating and sedative doses of ethanol (Bowers et al. 2001), while PKCδ knockout mice are insensitive to the ataxic effects of ethanol (Choi et al. 2008) and PKCε knockout
