Assembly of GABAA receptor subunits: Role of the δ subunit

Abstract

GABAA receptor channels (GABARs) composed of different combinations of rat α1, β1, γ2L, and δ subunits were expressed transiently in mouse fibroblast cells (L929 cells). Whole-cell recordings were obtained from transfected cells to determine which combinations of GABAR subunits formed functional receptor channels, and to compare the electrophysiological and pharmacological characteristics of GABAR channels expressed in the presence and absence of the δ subunit. Only α1β1γ2L, α1β1γ2Lδ, and α1β1δ subunit combinations assembled to form functional GABAR channels and the presence of the δ-subunit slowed the rate of acute desensitization of GABA-evoked current during GABA application and the rate of recovery of GABA-evoked current following GABA application. These three different GABAR channel isoforms also showed distinct pharmacological profiles with differential sensitivity to block by zinc. Zinc was a potent blocker of α1β1δ GABAR channels, a moderate-strength blocker of α1β1γ2Lδ GABAR channels, and did not block the α1β1γ2L GABAR channels. These findings suggest that GABAR isoforms containing the δ subunit constitute a novel GABAR channel with distinct electrophysiological and pharmacological characteristics.