Differential effects of glutamate transporter inhibitors on the global electrophysiological response of astrocytes to neuronal stimulation
Differential effects of glutamate transporter inhibitors on the global electrophysiological response of astrocytes to neuronal stimulation
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DOI：
10.1016/j.brainres.2008.09.014
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发表时间：
2008-11-13
期刊：
影响因子：
2.9
通讯作者：
Chatton, Jean-Yves
中科院分区：
文献类型：
--
作者：
Bernardinelli, Yann;Chatton, Jean-Yves
星形胶质细胞负责在神经元活动期间调节细胞外谷氨酸和钾水平。谷氨酸清除由星形胶质细胞中的谷氨酸转运子亚型谷氨酸转运子1和谷氨酸-天冬氨酸转运子处理。DL-苏型-β-苄氧基天冬氨酸（TBOA）和二氢红藻氨酸（DHK）被广泛用作神经胶质谷氨酸转运活性的抑制剂。使用全细胞记录，我们的特点是这两种转运蛋白抑制剂对传入诱发的星形胶质细胞电流在急性皮层切片的3周龄大鼠的影响。当神经元传入受到刺激时，被动星形胶质细胞会产生快速的内向电流，然后产生持续的尾电流。第一个电流对应于谷氨酸转运体电流。该电流被两种抑制剂和河豚毒素抑制。尾电流是一种内向钾电流，因为它被钡阻断。除了抑制转运体电流，TBOA强烈增强尾电流。这种效应是钡敏感的，可能是由于细胞外钾水平的上升和增加胶质细胞钾的摄取。与TBOA不同，DHK没有增强尾电流，而是抑制it. This结果表明，除了抑制谷氨酸转运，DHK防止星形胶质细胞钾的摄取，可能是通过阻断内向整流通道。这项研究表明，在脑切片中，谷氨酸转运体抑制剂发挥复杂的作用，不能仅仅归因于谷氨酸转运抑制。(C)2008 Elsevier B. V.保留所有权利。
Astrocytes are responsible for regulating extracellular levels of glutamate and potassium during neuronal activity. Glutamate clearance is handled by glutamate transporter subtypes glutamate transporter 1 and glutamate-aspartate transporter in astrocytes. DL-threo-beta-benzyloxyaspartate (TBOA) and dihydrokainate (DHK) are extensively used as inhibitors of glial glutamate transport activity. Using whole-cell recordings, we characterized the effects of both transporter inhibitors on afferent-evoked astrocyte currents in acute cortical slices of 3-week-old rats. When neuronal afferents were stimulated, passive astrocytes responded by a rapid inward current followed by a persistent tail current. The first current corresponded to a glutamate transporter current. This current was inhibited by both inhibitors and by tetrodotoxin. The tail current is an inward potassium current as it was blocked by barium. Besides inhibiting transporter currents, TBOA strongly enhanced the tail current. This effect was barium-sensitive and might be due to a rise in extracellular potassium level and increased glial potassium uptake. Unlike TBOA, DHK did not enhance the tail current but rather inhibited it. This result suggests that, in addition to inhibiting glutamate transport, DHK prevents astrocyte potassium uptake, possibly by blockade of inward-rectifier channels. This study revealed that, in brain slices, glutamate transporter inhibitors exert complex effects that cannot be attributed solely to glutamate transport inhibition. (C) 2008 Elsevier B.V. All rights reserved.