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Description
Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. There are two major classes of GABA receptors: the GABAA and the GABAB subtype of receptors. GABAA-Rs are important therapeutic targets for a range of sedative, anxiolytic, and hypnotic agents and are implicated in several diseases including epilepsy, anxiety, depression, and sub-stance abuse. The GABAA-R is a multimeric subunit complex. To date six alphas, four betas and four gammas, plus alternative splicing variants of some of these subunits, have been identified (Olsen and Tobin, 1990, Whiting et al., 1999, Ogris et al., 2004). Injection in oocytes or mammalian cell lines of cRNA coding for alpha and beta subunits results in the expression of functional GABAA-Rs sensitive to GABA. However, coexpression of a gamma subunit is required for benzodiazepine modulation. It has recently been suggested that PKC regulates the sensitivity of GABAA alpha1beta2gamma2 receptors to ethanol and benzodiazepines through phosphorylation of serine 327 in the large intracellular loop of gamma2 (Qi et al., 2007)