Neurosteroid pregnenolone sulfate antagonizes electrophysiological responses to GABA in neurons.
Our earlier biochemical studies suggested that the neurosteroid pregnenolone sulfate (PS) may reduce gamma-aminobutyric acid (GABA) action at the Cl- channel associated with GABAA receptors. In the present electrophysiological study the interaction of PS with the GABAA receptor was tested, using whole-cell voltage-clamp recordings from isolated cerebral cortical neurons of neonatal rats. At micromolar concentrations PS reversibly inhibited GABA-induced current, behaving as an allosteric receptor antagonist.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D005442:Flumazenil / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D011284:Pregnenolone / Q000494:pharmacology*; D051381:Rats; D013256:Steroids / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D013256:Steroids; C018370:pregnenolone sulfate; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D011284:Pregnenolone; D010424:Pentobarbital; D001640:Bicuculline