The role of GABA_A receptor biogenesis, structure and function in epilepsy

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABA_A (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABA_A receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABA_A receptor subunits. Moreover, a number of recent studies on GABA_A receptor mutations associated with epilepsy have further enhanced our understanding of GABA_A receptor biogenesis, structure and function.