The GABAA-R are members of the Cys-loop pentameric LGIC superfamily, including nicotinic acetylcholine receptors, inhibitory glycine receptors, and ionotropic 5-HT3 (serotonin) receptors. They differ in structure from two additional LGIC families: the tetrameric glutamate receptors, and the trimeric purine receptors (see mini-reviews on these families in this volume). All of the 44 subunit members of the Cys-loop pentameric LGIC superfamily (Collingridge et al., 2008) show sequence homology on the order of 30 % identity, but even greater similarity at the level of secondary and tertiary structure. All are organized as pentameric membrane-spanning proteins surrounding a central pore which forms the ion channel through the membrane. They all use similar sequences and functional domains to establish membrane topology, ion channel structure, agonist binding sites, and even binding sites for diverse allosteric ligands (Corringer et al., 2000; Sine & Engel, 2006; Sigel & Buhr, 1997; Li et al., 2006; Bali & Akabas,2004; Hosie et al., 2006). Each subunit consists of a long N-terminal extracellular hydrophilic region, followed by four trans-membrane (M) α-helices with a large intracellular loop between M3 and M4, and
