Fig. 1. Organization of the γ-aminobutyric acid type A (GABAA) receptor. (A ) A subunit of the GABAAreceptor contains a long aminoterminal region, followed by three transmembrane domains (M1–M3), a long cytoplasmic loop, the fourth membrane-spanning segment (M4), and a short carboxyterminal domain. The M2 domain is a major contributor to the central pore. (B ) Topology of a subunit showing the region of the subunit contributing to the transmitter binding site (G). The neurosteroid and etomidate binding sites are located in the membrane-spanning domains. A functional receptor is formed of five homologous subunits organized around a central Cl−conducting pore. (C ) A top view (cross section) of the receptor demonstrating the principal locations of the transmitter binding sites (G) at the β-α subunit interfaces. The β subunit contributes the primary (or, “+”) side and the α subunit contributes the complementary (or, “−”) side of the transmitter binding site. The receptor contains two pairs of β and α subunits. The fifth subunit (blue area ) may be a third α or β subunit, or a γ, δ, or ε subunit. The nature of the subunit in the fifth position can have a strong effect on the functional properties of the receptor. Benzodiazepines interact with a site at the α-γ subunit interface. Some receptors (e.g. , ρ subunit-containing) can form as homopentamers having the same major structural features.