Vesicular glutamate transporter-dependent glutamate release from astrocytes
Vesicular glutamate transporter-dependent glutamate release from astrocytes
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DOI：
10.1523/jneurosci.3770-03.2004
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发表时间：
2004-03-17
影响因子：
5.3
通讯作者：
Parpura, V
中科院分区：
文献类型：
--
作者：
Montana, V;Ni, YC;Parpura, V
星形胶质细胞因其细胞内钙离子浓度的变化而表现出兴奋性，这导致谷氨酸的释放，而谷氨酸又可以向邻近的神经元发出信号。这种谷氨酸介导的星形胶质细胞-神经元信号发生在星形胶质细胞的生理细胞内钙离子水平，并包括突触传递的调节。星形胶质细胞释放谷氨酸的机制很可能是胞吐作用，因为星形胶质细胞表达可溶性N-乙基马来酰亚胺敏感的融合蛋白附着蛋白受体复合体的蛋白质组分，包括突触素2、突触素和23 kDa的突触体相关蛋白。虽然这些蛋白介导了星形胶质细胞钙依赖的谷氨酸释放，但目前还不清楚星形胶质细胞是否表达对囊泡再充盈至关重要的功能性囊泡谷氨酸转运体(VGLUT)。在这里，我们发现在培养和新鲜分离的星形胶质细胞中，存在脑特异性的钠依赖的无机磷酸共转运体和分化相关的钠依赖的无机磷酸共转运体，它们最近被鉴定为VGLUT 1和2。间接免疫细胞化学显示VGLUT免疫反应在整个细胞体和突起呈点状分布，而VGLUT的药理抑制被机械地取消，并由激动剂诱导星形胶质细胞释放钙依赖的谷氨酸。综上所述，这些数据表明VGLUT在星形胶质细胞胞吐谷氨酸释放中起着功能作用。
Astrocytes exhibit excitability based on variations of their intracellular Ca2+ concentrations, which leads to glutamate release, that in turn can signal to adjacent neurons. This glutamate-mediated astrocyte - neuron signaling occurs at physiological intracellular Ca2+ levels in astrocytes and includes modulation of synaptic transmission. The mechanism underlying Ca2+-dependent glutamate release from astrocytes is most likely exocytosis, because astrocytes express the protein components of the soluble N-ethyl maleimide-sensitive fusion protein attachment protein receptors complex, including synaptobrevin 2, syntaxin, and synaptosome-associated protein of 23 kDa. Although these proteins mediate Ca2+-dependent glutamate release from astrocytes, it is not well understood whether astrocytes express functional vesicular glutamate transporters (VGLUTs) that are critical for vesicle refilling. Here, we find in cultured and freshly isolated astrocytes the presence of brain-specific Na+-dependent inorganic phosphate cotransporter and differentiation-associated Na+-dependent inorganic phosphate cotransporter that have recently been identified as VGLUTs 1 and 2. Indirect immunocytochemistry showed a punctate pattern of VGLUT immunoreactivity throughout the entire cell body and processes, whereas pharmacological inhibition of VGLUTs abolished mechanically and agonist-evoked Ca2+-dependent glutamate release from astrocytes. Taken together, these data indicate that VGLUTs play a functional role in exocytotic glutamate release from astrocytes.