GABAA receptor subunits contain phosphorylation sites for many protein kinases including PKC, PKA, and fyn kinase. Phosphorylation can alter receptor function directly by changing its conformation and/or indirectly by altering receptor expression. Since PKA and fyn kinase alter GABAA receptor function, it is possible that these protein kinases are also involved in trafficking of GABAA receptors. For example, chronic activation of PKA in cerebellar granule cells increases cell surface expression of GABAA receptor α1 subunit (Ives et al. 2002). In addition, ethanol exposure alters expression and translocation of PKA (Diamond and Gordon 1994; Newton and Messing 2006; Pandey 1998). Hence, it is likely that PKA is also involved in trafficking of GABAA receptors following ethanol exposure. However, to date, the role of these protein kinases has not yet been studied in trafficking of GABAA receptors, especially following ethanol exposure. Future studies will determine the specific role of various protein kinases in GABAA receptor trafficking and resolve the precise mechanisms that account for alterations in GABAA receptor function and expression following chronic ethanol administration.
