Ethanol effects on electrophysiological properties of astrocytes in striatal brain slices
Ethanol effects on electrophysiological properties of astrocytes in striatal brain slices
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DOI：
10.1016/j.neuropharm.2006.05.035
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发表时间：
2006-12-01
影响因子：
4.7
通讯作者：
Lovinger, David M.
中科院分区：
文献类型：
--
作者：
Adermark, Louise;Lovinger, David M.
已知乙醇（EtOH）可以改变神经元生理，但对这种药物对神经胶质功能的作用知之甚少。为此，我们利用大鼠脑切片检测了乙醇对纹状体星形胶质细胞静息和电压激活膜电流的急性影响。暴露于50 mM EtOH 10分钟可使斜坡电导降低20%，输入电阻增加25%，电容降低38%，但不影响静息膜电位。超极化脉冲产生的电流在被动星形胶质细胞中以浓度依赖的方式被抑制，而在复杂星形胶质细胞或神经元中未观察到明显的EtOH效应。当细胞内的KCl被CsCl取代时，EtOH效应被阻断，但当细胞内钙与BAPTA螯合时，EtOH效应不被阻断。当细胞内高CaCl2或细胞外卡贝诺洛酮偶联阻断间隙连接时，EtOH效应持续存在，但减弱。有趣的是，当间隙连接打开时，EtOH效应基本上是不可逆的，但当间隙连接关闭时，EtOH效应是完全可逆的。乙醇也减少了路西法黄染料通过移液管填充的单个胶质细胞向其他细胞的扩散。这些数据表明，EtOH抑制了一个钙不敏感的钾通道，很可能是一个被动的钾通道，但也以一种在乙醇退出后持续的方式影响间隙连接耦合。星形胶质细胞在脑钾稳态中起关键作用，因此EtOH对星形胶质细胞功能的影响可能影响神经元活动。Elsevier Ltd.出版。
Ethanol (EtOH) is known to alter neuronal physiology, but much less is known about the actions of this drug on glial function. To this end, we examined acute effects of ethanol on resting and voltage-activated membrane currents in striatal astrocytes using rat brain slices. Ten minutes exposure to 50 mM EtOH reduced slope conductance by 20%, increased input resistance by 25% and decreased capacitance by 38% but did not affect resting membrane potential. Current generated by a hyperpolarizing pulse was inhibited in a concentration dependent manner in passive astrocytes, while no significant EtOH effect was observed in complex astrocytes or neurons. The EtOH effect was blocked when intracellular KCl was replaced with CsCl, but not during chelation of intracellular calcium with BAPTA. During blockage of gap junction coupling with high intracellular CaCl2 or extracellular carbenoxolone the EtOH effect persisted but was reduced. Interestingly, EtOH effects were largely irreversible when gap junctions were open, but were fully reversible when gap junctions were closed. Ethanol also reduced the spread to other cells of Lucifer Yellow dye from individual glia filled via the patch pipette. These data suggest that EtOH inhibits a calcium-insensitive potassium channel, most likely a passive potassium channel, but also affects gap junction coupling in a way that is sustained after ethanol withdrawal. Astrocytes play a critical role in brain potassium homeostasis, and therefore EtOH effects on astrocytic function could influence neuronal activity. Published by Elsevier Ltd.