Mistry D K, Cottrell G A
Department of Biology and Preclinical Medicine, University of St Andrews.
Exp Physiol. 1990 Mar;75(2):199-209. doi: 10.1113/expphysiol.1990.sp003394.
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.
研究了一种合成类固醇和一种内源性类固醇对培养的离体小鼠脊髓神经元GABAA受体的作用。低剂量的alphaxalone可使GABA诱发的全细胞电流可逆性增加。高剂量（10 - 50微摩尔）的alphaxalone通过压力喷射到脊髓神经元上时，也可直接诱发膜氯化物电流。此类电流可被荷包牡丹碱（一种GABAA拮抗剂）可逆性抑制，并被苯巴比妥增强。5β-孕烷-3α-醇-20-酮，一种孕酮代谢产物，剂量依赖性地增强GABA诱发的全细胞电流幅度。使用脊髓神经元的外侧外翻膜片在单通道水平研究了增强机制。类固醇对GABAA受体的主要作用似乎与巴比妥类药物相似，即它们延长了GABA激活的通道开放爆发。美解眠对GABAA受体有拮抗作用，在相似程度上抑制GABA和戊巴比妥诱发的全细胞电流。
