Effects of subunit types of the cloned GABAA receptor on the response to a neurosteroid.
Combinations of cloned GABAA receptor subtypes, having the subunit combinations alpha i + beta 1 or alpha i + beta 1 + gamma 2 (i = 1, 2, 3), were expressed in Xenopus oocytes. The endogenous steroid 3 alpha-hydroxy-5 alpha-pregnan-20-one potentiates GABA currents induced therein by GABA. This potentiation was greater in the alpha 1 + beta and alpha 3 + beta 1 than in the alpha 2 + beta 1 combinations. The presence of the gamma 2-subunit increased the steroid potency in alpha 1 + beta 1 and alpha 2 + beta 1, but the combination alpha 3 + beta 1 + gamma 2 became much less steroid-sensitive. It is concluded that the steroid modification of the GABAA receptor is strongly influenced by the alpha- and the gamma 2-subunit types.
MRC Molecular Neurobiology Unit, MRC Centre, Cambridge, U.K.
R
R
Shingai
M L
ML
Sutherland
E A
EA
Barnard
D000818:Animals; D003001:Cloning, Molecular; D004594:Electrophysiology; D015870:Gene Expression; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D011280:Pregnanolone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D014981:Xenopus / Q000378:metabolism*
D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D011280:Pregnanolone