Protein phosphorylation regulates GABAA receptor function under numerous physiologic conditions (Brandon et al. 2000; Kellenberger et al. 1992; Krishek et al. 1994; Kumar et al. 2005; Leidenheimer et al. 1992; Poisbeau et al. 1999), including alcoholism and epilepsy (Kumar et al. 2006; Niimura et al. 2005; Rakhade et al. 2008). Several protein kinases, including PKC and PKA, have consensus sites on GABAA receptor subunits and can phosphorylate these subunits (Brandon et al. 2000; McDonald and Moss 1997). Phosphorylation of GABAA receptor subunits can modify GABA binding to its receptor (Oh et al. 1999), channel conductance, and possibly internalization (Moss and Smart 2001). Additionally, studies using genetically modified mice clearly demonstrate that the pharmacological and behavioral effects of ethanol are partially mediated by PKC activity (Choi et al. 2008; Harris et al. 1995; Hodge et al. 1999; Proctor et al. 2003).
