Receptor-mediated glutamate release from volume sensitive channels in astrocytes

Receptor-mediated glutamate release from volume sensitive channels in astrocytes
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DOI:
10.1073/pnas.0506382102
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发表时间:
2005-11-08
影响因子:
11.1
通讯作者:
Nedergaard, M
Nedergaard, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Takano, T;Kang, J;Nedergaard, M

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一些研究表明,星形胶质细胞响应受体激活释放谷氨酸,这导致局部突触活动的调节。星形胶质细胞谷氨酸释放是Ca 2+依赖性的,并与含谷氨酸囊泡的胞吐作用一起发生。然而,星形胶质细胞含有毫摩尔浓度的胞质谷氨酸盐,并表达可渗透小阴离子(如谷氨酸盐)的通道。在这里,我们测试的想法,星形胶质细胞响应受体刺激的细胞体积的动态变化,导致体积敏感性通道激活,和流出的胞质谷氨酸。共聚焦成像和全细胞记录表明,星形胶质细胞表现出短暂的Ca 2+依赖性细胞体积增加,激活谷氨酸渗透通道。HPLC分析表明,谷氨酸与其他氨基酸骨结合释放。我们的观察结果表明,体积敏感通道可能构成一个以前未表征的星形胶质细胞-神经元相互作用的调制目标。
Several lines of work have shown that astrocytes release glutamate in response to receptor activation, which results in a modulation of local synaptic activity. Astrocytic glutamate release is Ca2+-dependent and occurs in conjunction with exocytosis of glutamate containing vesicles. However, astrocytes contain a millimolar concentration of cytosolic glutamate and express channels permeable to small anions, such as glutamate. Here, we tested the idea that astrocytes respond to receptor stimulation by dynamic changes in cell volume, resulting in volume-sensitive channel activation, and efflux of cytosolic glutamate. Confocal imaging and whole-cell recordings demonstrated that astrocytes exhibited a transient Ca2+-dependent cell volume increase, which activated glutamate permeable channels. HPLC analysis revealed that glutamate was released in conjunction with other amino acid os-molytes. Our observations indicate that volume-sensitive channel may constitute a previously uncharacterized target for modulation of astrocyte-neuronal interactions.