Actions of steroids and bemegride on the GABAA receptor of mouse spinal neurones in culture.
The effects of a synthetic and an endogenous steroid were studied on the GABAA receptors of isolated mouse spinal neurones, maintained in culture. Low doses of alphaxalone reversibly increased GABA-evoked whole-cell currents. Alphaxalone at higher doses (10-50 microM), when pressure ejected onto spinal neurones, also directly evoked a membrane chloride current. Such currents were reversibly suppressed by bicuculline (a GABAA antagonist) and enhanced by phenobarbitone. 5 beta-Pregnan-3 alpha-ol-20-one, a progesterone metabolite, dose-dependently potentiated the amplitude of GABA-evoked whole-cell currents. The mechanism of potentiation was examined at the single-channel level using outside-out patches from spinal neurones. The main action of the steroid on the GABAA receptor appears to be similar to that found for barbiturates, in that they prolonged GABA-activated bursts of channel openings. Bemegride had an antagonistic action on the GABAA receptor, suppressing both GABA- and pentobarbitone-evoked whole-cell currents to similar extents.
Mistry
D K
DK
Department of Biology and Preclinical Medicine, University of St Andrews.
Cottrell
G A
GA
D000818:Animals; D001534:Bemegride / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D058787:GABA-A Receptor Antagonists; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011277:Pregnanediones / Q000494:pharmacology*; D011278:Pregnanes / Q000494:pharmacology*; D011280:Pregnanolone / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology
D058787:GABA-A Receptor Antagonists; D011277:Pregnanediones; D011278:Pregnanes; D011963:Receptors, GABA-A; D001534:Bemegride; C006477:alphaxalone; D011280:Pregnanolone; D001640:Bicuculline