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首页> 外文期刊>Brain research >Differential effects of glutamate transporter inhibitors on the global electrophysiological response of astrocytes to neuronal stimulation.
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Differential effects of glutamate transporter inhibitors on the global electrophysiological response of astrocytes to neuronal stimulation.

机译：谷氨酸转运蛋白抑制剂对星形胶质细胞对神经元刺激的整体电生理反应的不同作用。

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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.
机译：在神经元活动期间，星形胶质细胞负责调节细胞外谷氨酸和钾的水平。通过星形胶质细胞中的谷氨酸转运蛋白亚型谷氨酸转运蛋白1和谷氨酸-天冬氨酸转运蛋白来处理谷氨酸清除。 DL-苏-β-苄氧基天冬氨酸（TBOA）和二氢海藻酸酯（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，我们表征了这两种转运蛋白抑制剂对3周龄大鼠急性皮质切片中传入诱发星形胶质细胞电流的影响。当刺激神经元传入神经时，被动星形胶质细胞通过快速的内向电流和持续的尾电流反应。第一电流对应于谷氨酸转运蛋白电流。该电流被抑制剂和河豚毒素均抑制。尾电流是被钡阻挡的内向钾电流。除了抑制运输电流，TBOA还大大增强了尾电流。该作用对钡敏感，可能是由于细胞外钾水平升高和神经胶质钾摄取增加所致。与TBOA不同，DHK并未增强尾电流，而是抑制了尾电流。该结果表明，除了抑制谷氨酸的转运外，DHK还可能通过阻断内向整流器通道来阻止星形胶质细胞钾的吸收。这项研究表明，在脑片中，谷氨酸转运蛋白抑制剂发挥了复杂的作用，而这不能仅仅归因于谷氨酸转运抑制。

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