Etomidate, propofol and diazepam potentiate GABA-evoked GABAA currents in a cell line derived from human glioblastoma
Etomidate, propofol and diazepam potentiate GABA-evoked GABAA currents in a cell line derived from human glioblastoma
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DOI：
10.1016/j.ejphar.2014.12.001
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发表时间：
2015-02-05
影响因子：
5
通讯作者：
Birnir, Bryndis
中科院分区：
文献类型：
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作者：
Babateen, Omar;Jin, Zhe;Birnir, Bryndis
GABA（A）受体是由GABA开放的五聚体氯离子通道。我们筛选了一个来源于人胶质母细胞瘤的细胞系U3047 MG，用于表达GABA（A）受体亚单位亚型和形成功能性离子通道。我们在U3047 MG细胞系中鉴定了GABA（A）受体亚基α 2、α 3、α 5、β 1、β 2、β 3、δ、γ 3、pi和θ mRNA。记录全细胞GABA激活电流，GABA激活电流的半数最大浓度（EC 50）为36 μ M。电流被THIP（4，5，6，7-四氢异恶唑并[5，4-c]吡啶-3-醇）激活，并被苯二氮卓类地西泮（1 μ M）和全身麻醉剂依托咪酯和普罗洛尔（50 μ M）增强。与至少含有α 3 β 3 θ亚基的表达GABA（A）受体一致，受体对依托咪酯高度敏感（EC 50 =55 nM）。免疫细胞化学鉴定了α 3和β 3亚基蛋白的表达。我们的研究结果表明，神经胶质细胞系中的GABA（A）受体是功能性的，并受到经典GABA（A）受体药物的调节。U3047 MG细胞系可作为研究神经胶质细胞GABA（A）受体功能和药理学的模型系统。(C)2014爱思唯尔有限公司版权所有。
GABA(A) receptors are pentameric chloride ion channels that are opened by GABA. We have screened a cell line derived from human glioblastoma, U3047MG, for expression of GABA(A) receptor subunit isoforms and formation of functional ion channels. We identified GABA(A) receptors subunit alpha 2, alpha 3, alpha 5, beta 1, beta 2, beta 3, delta, gamma 3, pi, and theta mRNAs in the U3047MG cell line. Whole-cell GABA-activated currents were recorded and the half-maximal concentration (EC50) for the GABA-activated current was 36 mu M. The currents were activated by THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and enhanced by the benzodiazepine diazepam (1 mu M) and the general anesthetics etomidate and propolol (50 mu M). In line with the expressed GABA(A) receptors containing at least the alpha 3 beta 3 theta subunits, the receptors were highly sensitive to etomidate (EC50=55 nM). Immunocytochemistry identified expression of the alpha 3 and beta 3 subunit proteins. Our results show that the GABA(A) receptors in the glial cell line are functional and are modulated by classical GABA(A) receptor drugs. We propose that the U3047MG cell line may be used as a model system to study GABA(A) receptors function and pharmacology in glial cells. (C) 2014 Elsevier B.V. All rights reserved.