Gamma-aminobutyric acid (GABA)-gated ion channels are widely distributed in the mammalian brain and are major mediators of inhibitory synaptic transmission. A typical GABA_A ion channel has a pentameric structure consisting of 5 protein subunits, often α, β and γ, combining to form a central ion conducting pore across the cell membrane. In humans there are six genes that encode α subunits, three that encode β, three that encode γ, and an additional seven genes that encode other subunits whose function is less-well understood than the α, β and γ subunits. GABA_A ion channels open and close in response to secretion of GABA from presynaptic terminals. GABA_A α5 channels are typically comprised of α5, β3, and γ2 subunits and this combination is preferentially expressed in the mammalian hippocampus (Wisden et al., 1992). Much pharmaceutical research interest has focused on α5-selective “inverse agonists” at the benzodiazepine (BZ) site, which decrease the current elicited by a concentration of GABA that produces a 20% response, i.e. an EC20 (Atack et al. 2006, Dawson et al. 2006). These compounds show promise as dementia treatments because in animal models they enhance cognition with minimal proconvulsant or anxiogenic side-effects.