Background Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABA causes a hyperpolarization of the membrane through the opening of a Cl- channel associated with the GABAa Receptor (GABAa-R) subtype. 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 substance abuse. The GABAa-R is a multimeric subunit complex. Six alphas, four betas and four gammas, as well as alternative splicing variants of some of these subunits, have been identified. Injection in oocytes or mammalian cell lines of cRNA coding for a- and b-subunits results in the expression of functional GABAa-Rs sensitive to GABA. However, coexpression of a g-subunit is required for benzodiazepine modulation. The various effects of the benzodiazepines in brain may also be mediated via different a-subunits of the receptor. Lastly, phosphorylation of b-subunits of the receptor has been shown to modulate GABAa-R function. |
Reference
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