Protease activated receptor 1-induced glutamate release in cultured astrocytes is mediated by Bestrophin-1 channel but not by vesicular exocytosis

培养的星形胶质细胞中,蛋白酶激活受体1诱导的谷氨酸释放是由Bestrophin-1通道介导的,而不是由囊泡胞吐作用介导的。

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Abstract

BACKGROUND: Glutamate is the major transmitter that mediates the principal form of excitatory synaptic transmission in the brain. It has been well established that glutamate is released via Ca2+-dependent exocytosis of glutamate-containing vesicles in neurons. However, whether astrocytes exocytose to release glutamate under physiological condition is still unclear. FINDINGS: We report a novel form of glutamate release in astrocytes via the recently characterized Ca2+-activated anion channel, Bestrophin-1 (Best1) by Ca2+ dependent mechanism through the channel pore. We demonstrate that upon activation of protease activated receptor 1 (PAR1), an increase in intracellular Ca2+ concentration leads to an opening of Best1 channels and subsequent release of glutamate in cultured astrocytes. CONCLUSIONS: These results provide strong molecular evidence for potential astrocyte-neuron interaction via Best1-mediated glutamate release.

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