Low doses of ethanol and a neuroactive steroid positively interact to modulate rat GABAA receptor function
Low doses of ethanol and a neuroactive steroid positively interact to modulate rat GABAA receptor function
复制标题
DOI：
10.1113/jphysiol.2002.032300
复制
发表时间：
2003-02-01
影响因子：
5.5
通讯作者：
Steinbach, JH
中科院分区：
文献类型：
--
作者：
Akk, G;Steinbach, JH
中枢神经系统中的快速抑制反应由GABA受体介导。GABA（A）受体的激活和功能可以通过多种化合物调节，包括苯二氮卓类、巴比妥类和神经活性类固醇。乙醇对GABAA受体功能的调节在一些研究中观察到，但不是所有研究。我们已经研究了乙醇浓度对应于光中毒的重组GABAA受体的功能，含有α 1 β 2 γ 2亚基的效果。实验在存在和不存在低的阈下浓度的神经活性类固醇的情况下进行。结果表明，在类固醇存在下，0.05%（9 mm）乙醇通过增加通道平均开放持续时间增强GABAA受体功能。未观察到对通道关闭持续时间的影响。这些数据表明，乙醇影响通道关闭，对GABA受体的亲和力或通道开放速率常数没有影响。
Fast inhibitory responses in the central nervous system are mediated by the GABA, receptor. The activation and function of the GABA(A) receptor can be modulated by a variety of compounds including benzodiazepines, barbiturates and neuroactive steroids. Modulation of the GABAA receptor function by ethanol has been observed in some but not all studies. We have studied the effect of ethanol at concentrations corresponding to light intoxication on the function of the recombinant GABAA receptor containing alpha1beta2gamma2 subunits. The experiments were performed both in the absence and presence of low, subthreshold concentrations of a neuroactive steroid. The results demonstrate that, in the presence of the steroid, 0.05 % (9 mm) ethanol potentiates the GABAA receptor function by increasing the channel mean open duration. No effect was observed on the channel closed time durations. The data suggest that ethanol influences channel closing with no effect on the affinity of the receptor for GABA or the channel opening rate constant.