Recent studies have shown that fyn kinase is involved in ethanol-induced changes in GABAA receptor function. For example, over-expression of fyn kinase reduces sedative-hypnotic sensitivity to ethanol (Boehm et al. 2004a). Furthermore, fyn kinase knockout mice are less sensitive to the sedative-hypnotic effects of etomidate (an intravenous anesthetic, selective for β2- and/or β3-GABAA receptors; see Jurd et al. 2003) suggesting that fyn kinase alters GABAA receptor function by acting on GABAA receptor β2 and β3 subunits (Boehm et al. 2004c). Similarly, in vitro and in vivo studies have implicated tyrosine kinase in ethanol-mediated alterations of GABAA receptor function. Ethanol exposure increases tyrosine kinase phosphorylation of the GABAA receptor subunits α1, β2, and γ2 in mouse cultured cortical neurons (Marutha Ravindran and Ticku 2006) and rat cerebral cortex (Marutha Ravindran et al. 2007). In addition, tyrosine kinase phosphorylation of GABAA receptor γ2 subunit regulates GABAA receptor surface expression and function (Kittler et al. 2008). Hence, it appears that multiple kinases are involved in ethanol-mediated alteration in GABAA receptor function. Therefore, studies of the interactions of GABAA receptors with these kinases will lead to a better understanding of ethanol actions on GABAA receptors.
