Sooksawate T, Simmonds M A
Department of Pharmacology, The School of Pharmacy, University of London, UK.
Neuropharmacology. 1998 Sep;37(9):1103-10. doi: 10.1016/s0028-3908(98)00113-0.
The effects of increased membrane cholesterol on the potentiation of GABA(A) currents by pregnanolone (5beta-pregnan-3alpha-ol-20-one), allopregnanolone (5alpha-pregnan-3alpha-ol-20-one), alphaxalone (5alpha-pregnan-3alpha-ol-11,20-dione) and propofol were investigated in acutely dissociated rat hippocampal neurones using the whole-cell patch clamp technique. Cholesterol enrichment of the neurones, isolated from 10 to 16-day-old Wistar rat brains, was achieved by incubation with cholesterol + phosphatidylcholine liposomes. Cholesterol enrichment (25.8+/-3.4%) reduced the potentiation of GABA(A) currents by pregnanolone (0.3 and 1 microM), allopregnanolone (1 microM) and alphaxalone (1 microM) but the potentiation of GABA(A) currents by propofol (5 microM) was not affected. Acute application of cholesterol (1 microM) did not significantly change the potentiation of GABA(A) currents by pregnanolone (1 microM). These results suggest that cholesterol within the neuronal membrane may compete with neurosteroids for their sites of action on the GABA(A) receptor or modulate the potentiating effect of the neurosteroids in some other ways.
运用全细胞膜片钳技术，在急性分离的大鼠海马神经元中研究了膜胆固醇增加对孕烷醇酮（5β-孕烷-3α-醇-20-酮）、别孕烷醇酮（5α-孕烷-3α-醇-20-酮）、α-香豆素（5α-孕烷-3α-醇-11,20-二酮）和丙泊酚增强γ-氨基丁酸A（GABA(A)）电流作用的影响。从10至16日龄Wistar大鼠脑部分离的神经元，通过与胆固醇+磷脂酰胆碱脂质体孵育实现胆固醇富集。胆固醇富集（25.8±3.4%）降低了孕烷醇酮（0.3和1微摩尔）、别孕烷醇酮（1微摩尔）和α-香豆素（1微摩尔）对GABA(A)电流的增强作用，但丙泊酚（5微摩尔）对GABA(A)电流的增强作用未受影响。急性应用胆固醇（1微摩尔）未显著改变孕烷醇酮（1微摩尔）对GABA(A)电流的增强作用。这些结果表明，神经元膜内的胆固醇可能与神经甾体竞争其在GABA(A)受体上的作用位点，或以其他方式调节神经甾体的增强作用。
