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A novel pathway mediating GABA-induced Ca2+ signaling in NG2

时间:2009-07-25 07:35来源:ion.ac.cn 作者:ion 阅读:

 

On July 13, 2009, the Journal of Cell Biology published a research article from the Institute of Neuroscience entitled "Ca2+ signaling evoked by activation of Na+ channels and Na+/Ca2+ exchangers is required for GABA-induced NG2 cell migration". This work was carried out by Xiao-ping Tong with other graduate students from the laboratory of Dr. Shumin Duan. The paper was highlighted in the ‘News in this issue’ section, with a short introduction entitled "Brain-repairing cells follow trail of GABA".

NG2 glial cells in the developing brain are known as oligodendrocyte progenitor cells which generate oligodendrocytes to produce myelin in the brain. These cells constitute a significant population of glial cells in the adult brain and may play an important role in repairing brain injury. NG2 cells express voltage-gated Na+ channels, but fail to produce typical action potentials. The physiological role of Na+ channels in these cells is unclear. Using multiple approaches, Tong et al. were able to provide convincing evidence that activation of GABAA receptors in NG2 cells increased intracellular Ca2+ through an unconventional pathway – activation of persistent Na+ channels and Na+/Ca2+ exchangers. This unique Ca2+ signaling pathway is further shown to be involved in GABA-induced chemotactic migration of NG2 cells. This Ca2+ entry through the non-inactivating Na+ channel and Na+/Ca2+ exchanger pathway in NG2 cells may be important for both physiological and pathological processes.

Article link: http://jcb.rupress.org/cgi/content/abstract/186/1/113 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 Correspondence to Shumin Duan: [email protected] 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 of prolonged 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.(责任编辑:泉水)
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