Structure and function of GABAC receptors: A comparison of native versus recombinant receptors

Abstract

In less than a decade our knowledge of the GABAC receptor, a new type of Cl--permeable ionotropic GABA receptor, has greatly increased based on studies of both native and recombinant receptors. Careful comparison of properties of native and recombinant receptors has provided compelling evidence that GABA receptor ρ-subunits are the major molecular components of GABAC receptors. Three distinct ρ-subunits from various species have been cloned and the pattern of their expression in the retina, as well as in various brain regions, has been established. The pharmacological profile of GABAC receptors has been refined and more specific drugs have been developed. Molecular determinants that underlie functional properties of the receptors have been assigned to specific amino acid residues in ρ-subunits. This information has helped determine the subunit composition of native receptors, as well as the molecular basis underlying subtle variations among GABAC receptors in different species. Finally, GABAC receptors play a unique functional role in retinal signal processing via three mechanisms: (1) slow activation; (2) segregation from other inhibitory receptors; and (3) contribution to multi-neuronal pathways.