Gamma-aminobutyric acid (GABA)-gated ion channels are widely distributed in the mammalian brain and are major mediators of inhibitory synaptic transmission. A typical GABAA ion channel has a pentameric structure consisting of 5 protein subunits, often alpha, beta and gamma, combining to form a central ion conducting pore across the cell membrane. In humans there are six genes that encode alpha subunits, three that encode beta, three that encode gamma, and an additional seven genes that encode other subunits whose function is less-well understood than the alpha, beta and gamma subunits. GABAA ion channels open and close in response to secretion of GABA from presynaptic terminals. GABAA alpha5 channels are typically comprised of alpha5, beta3, and gamma2 subunits and this combination is preferentially expressed in the mammalian hippocampus. Much pharmaceutical research interest has focused on alpha5-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. These compounds show promise as dementia treatments because in animal models they enhance cognition with minimal proconvulsant or anxiogenic side-effects.
|Product Type||Ion Channel Expressing Cell|
|Channel Type||Chloride Channel|
|Channel Subgroup||GABAa Receptor|