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JCB:神经递质GABA引起NG2 胶质细胞钙信号及细胞迁移新机制

来源:SIBS 2009-07-15 15:38

2009年7月13日国际杂志《细胞生物学期刊》(Journal of Cell Biology)发表了中国科学院上海生命科学研究院神经科学研究所段树民实验室童小萍等的研究论文“GABA通过激活钠通道和钠-钙交换通路而引起的钙信号对NG2胶质细胞迁移的作用”。同期杂志在“本期新闻”栏目以题为“脑修复细胞对GABA的跟随反应”的短文对该论文给予重点介绍。

NG2胶质细胞又被称为少突胶质前体细胞,在脑发育早期产生少突胶质细胞以形成中枢神经的髓鞘。在成熟脑内也有大量的NG2细胞, 可能对脑损伤后的髓鞘修复起重要作用。NG2胶质细胞的一个重要特征是象神经元一样表达钠通道,但这些钠通道却不能产生神经元那样的动作电位,因此NG2胶质细胞所表达的钠通道的功能一直不清楚。童小萍等应用多种手段研究表明NG2胶质细胞表达的钠通道有一种慢失活成份。进一步研究发现NG2胶质细胞对神经递质GABA的反应和非成熟神经元的反应一样,都是产生兴奋性去极化反应,并使细胞内钙升高。与非成熟神经元的反应不同的是,GABA引起的NG2细胞钙升高并不是通过钙通道的激活,而是由于激活了钠通道的慢失活成份,从而使细胞内钠升高,继而通过钠-钙交换体使细胞内钙升高。进一步研究表明这一新颖的钙升高通路对GABA引起的NG2胶质细胞在脑内的迁移起关键作用。这些发现不但揭示了NG2胶质细胞新颖的钙信号机制,对理解发育早期NG2细胞在脑内的迁移机理及脑损伤后NG2细胞向损伤区迁移并参与髓鞘修复的机理也具有重要意义。(生物谷Bioon.com)

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The Journal of Cell Biology, Vol. 186, No. 1, 113-128 doi:10.1083/jcb.200811071

Ca2+ signaling evoked by activation of Na+ channels and Na+/Ca2+ exchangers is required for GABA-induced NG2 cell migration

Xiao-ping Tong, Xiang-yao Li, Bing Zhou, Wanhua Shen, Zhi-jun Zhang, Tian-le Xu, and Shumin Duan

Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

NG2 cells originate from various brain regions and migrate to their destinations during early development. These cells express voltage-gated Na+channels but fail to produce typical action potentials. The physiological role of Na+ channels in these cells is unclear. We found that GABA induces membrane depolarization and Ca2+ elevation in NG2 cells, a process requiring activation of GABAA receptors, Na+ channels, and Na+/Ca2+exchangers (NCXs), but not Ca2+ channels. We have identified a persistent Na+ current in these cells that may underlie the GABA-induced pathway ofprolonged Na+ elevation, which in turn triggers Ca2+ influx via NCXs. This unique Ca2+ signaling pathway is further shown to be involved in the migration of NG2 cells. Thus, GABAergic signaling mediated by sequential activation of GABAA receptors, noninactivating Na+ channels, and NCXs may play an important role in the development and function of NG2 glial cells in the brain.

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