GABAC Receptors: Structure, Function and Pharmacology

In the vertebrate central nervous system (CNS), γ-aminobutyric acid (GABA) is the most widely distributed neurotransmitter (Sivilotti and Nistri 1991). Initially, GABA was found to activate bicuculline-sensitive CI− channels, but GABA-mediated activation of cation channels was discovered subsequently (see Bormann 1988, for review). This lead to the notion of GABAA and GABAB receptors, which was introduced by Hill and Bowery (1981). The GABAA receptor directly gates a CI− ionophore and has modulatory binding sites for benzodiazepines, barbiturates, neuosteroids and ethanol (Macdonald and Olson 1994; Bormann 1988). By contrast, GABAB receptors couple to Ca2+ and K+ channels via G-proteins and second-messenger systems (Bormann 1988; Bowery 1989; Bettler et al. 1998). They are activated by baclofen and resistant to drugs that modulate GABAA receptors.