Effects of subunit types of the cloned GABAA receptor on the response to a neurosteroid.

Abstract Combinations of cloned GABA A receptor subtypes, having the subunit combinations α 1 + s 1 or α 1 + s 1 + γ 2 (i = 1. 2. 3). were expressed in Xenopus oocytes. The endogenous steroid 3α-hydroxy-5α-pregnan-20-one potentiates GABA currents induced therein by GABA. This potentiation was greater in the α 1 + s and α 3 + s 1 than in the α 2 + s 1 combinations. The presence of thee γ2-subunit increased the steroid potency in α 1 + s 1 and α 2 + s 1, but the combination α 3 + s 1 + γ 2 became much less steroid-sensitive. It is concluded that the steroid modification of the GABA A receptor is strongly influenced by the α- and the γ2-subunit types.