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Title: GABA引起NG2胶质细胞钙升高及其对细胞迁移影响的机制研究
Author: 童小萍
Degree Level: 博士
Issued Date: 2009-04-03
Degree Grantor: 中国科学院上海生命科学研究院
Place of Degree Grantor: 上海生命科学研究院
Supervisor: 段树民
Keyword: NG2胶质细胞 ; 钙信号 ; γ-氨基丁酸 ; GABAA 受体 ; 钠通道 ; 钠-钙交换体 ; 趋化性迁移
Alternative Title: Ca2+ Signaling Evoked by Activation of Na+ Channels and Na+/Ca2+ Exchangers Is Required for GABA-Induced NG2 Cell Migration
Major: 神经生物学
Abstract: NG2胶质细胞作为少突胶质细胞的前体细胞,在成年哺乳动物的大脑内大量存在并广泛分布。这类细胞可以直接接受神经元的谷氨酸能(glutamatergic)和γ-氨基丁酸能(GABAergic)的突触支配。以往的研究表明NG2胶质细胞接受的谷氨酸能突触可以通过其表达的钙通透性AMPA受体而产生可塑性变化,然而对于GABA能神经元的输入有何意义目前尚不清楚。NG2胶质细胞表达电压依赖的钠通道,但却不能产生可扩布的动作电位,其生理功能也不清楚。我们的研究表明,γ-氨基丁酸(GABA)能够引起NG2胶质细胞膜的去极化反应并可产生细胞内的钙升高,这一过程主要是通过GABAA 受体、 钠通道以及钠-钙交换体(NCX)共同介导完成的。同时我们还证实了NG2细胞表达的非失活的钠通道(non-inactivating Na+ channel)对GABA引起的钠离子持续内流,并进一步激活钠-钙交换体从而最终导致胞内钙升高起着非常重要的作用。进一步的研究还发现,GABA引起钙升高这一非常规的信号通路对于NG2胶质细胞的趋化性迁移也有着重要的影响。因此,由GABA能信号介导的GABAA 受体、非失活的钠通道以及钠-钙交换体对于NG2细胞在大脑中的发育和功能可能具有重要的生理和病理意义。
English Abstract: NG2 glial cells are distributed extensively in the brain and receive glutamatergic and GABAergic inputs from neurons. They 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 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 GABA-induced chemotactic migration of NG2 cells. Thus, GABAergic signaling mediated by sequential activation of GABAA receptors, non-inactivating Na+ channels, and NCXs may play an important role in the development and function of NG2 glial cells in the brain.
Language: 中文
Content Type: 学位论文
URI: http://ir.sibs.ac.cn/handle/331001/2357
Appears in Collections:神经所(总)_学位论文

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Recommended Citation:
GABA引起NG2胶质细胞钙升高及其对细胞迁移影响的机制研究.童小萍[d].中国科学院上海生命科学研究院,2009.20-25
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