A mutant residue in the third transmembrane region of the GABA(A) alpha1 subunit causes increased agonistic neurosteroid responses.

ABSTRACT: Pregnane derived steroids have agonistic and antagonistic actions at GABA(A) receptors. Putative binding sites for agonistic neurosteroids are located within the transmembrane (TM) regions. A mutation within the rat α(1) TM3 region, S299C, caused the expressed receptors to have unusual and extreme sensitivity to agonistic neurosteroids. For mutant α1S299C receptors, with wild type β and γ subunits, expressed in Xenopus oocytes, steroids activated the GABA(A) receptors in the absence of GABA. Maximal steroid induced currents were about half of maximal GABA currents. The steroid activation was biphasic with EC(50)'s much lower than wild type, in subnanomolar and nanomolar concentrations, while the wild type had only one activation peak with near micromolar EC(50). These currents could be blo

SUBMITTER: Williams DB 

PROVIDER: S-EPMC3175280 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature