Trichloroethanol potentiates synaptic transmission mediated by gamma-aminobutyric acidA receptors in hippocampal neurons.
Trichloroethanol potentiates synaptic transmission mediated by gamma-aminobutyric acidA receptors in hippocampal neurons.
复制标题
DOI：
--
复制
发表时间：
1993-03
期刊：
影响因子：
--
通讯作者：
D. Lovinger;S. Zimmerman;M. Levitin;Mathew V. Jones;Neil L. Harrison
中科院分区：
文献类型：
--
作者：
D. Lovinger;S. Zimmerman;M. Levitin;Mathew V. Jones;Neil L. Harrison
我们在海马神经元细胞培养和脑片上观察了全麻药水合氯醛的活性代谢物三氯乙醇(TCEt)对外源性GABA和激活内源性GABA能传递的GABA受体介导的反应的作用。在TCEt存在下，外源性GABA激活的Cl-电流的幅度增加且延长，导致通过GABAA受体通道的总电荷净增加。GABA激活电流的延长以浓度依赖的方式增加，从0.2 mM增加到10 mM。0.5~10 mM的TCEt也可延长培养的GABA能神经元之间突触的抑制性突触后电流或激活海马片间神经元产生的抑制性突触后电流。1 mM及以上浓度的TCEt在以硫酸甲酯或葡萄糖酸盐为主要细胞内阴离子的神经元上产生一向外为-40 mV的小幅度电流，在充满氯-的神经元上向内定向。我们的观察表明，TCEt增强GABAA能传递；可能是通过增强GABAA受体的功能，类似于巴比妥类或类固醇麻醉药。这一作用可能有助于TCET的全身麻醉效应，该效应发生在给予水合氯醛之后。
We have examined the actions of trichloroethanol (TCEt), the active metabolite of the general anesthetic chloral hydrate, on responses mediated by gamma-aminobutyric acid (GABA)A receptors in response to application of exogenous GABA and activation of endogenous GABAergic transmission, by using hippocampal neurons in cell culture and in brain slices. In the presence of TCEt, Cl- current activated by exogenous GABA was both enhanced in amplitude and prolonged, leading to a net increase in total charge passing through GABAA receptor channels. Prolongation of GABA-activated current increased in magnitude in a concentration-dependent manner from 0.2 to 10 mM TCEt. Inhibitory postsynaptic currents produced at synapses between pairs of cultured GABAergic neurons or by activation of interneurons in hippocampal slices were also prolonged by TCEt, at concentrations from 0.5 to 10 mM. Application of TCEt at concentrations of 1 mM and above produced a small amplitude current which was directed outwardly at -40 mV in neurons in which methylsulfate or gluconate was the major intracellular anion and directed inwardly in neurons filled with Cl-. Our observations indicate that TCEt potentiates GABAergic transmission; presumably by potentiating the function of GABAA receptors in a manner similar to barbiturate or steroid anesthetics. This action is likely to contribute to the general anesthetic effect of TCEt which occurs after chloral hydrate administration.