TRPC1阴离子通道通过甲基增生谷氨酸受体mGluR1的激活
Sang Jeong Kim1, Yu Shin Kim, Joseph P Yuan
1Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA.
Nature
|November 14, 2003
概括
第I组甲基酸盐受体 (mGluRs) 通过TRPC1离子通道激活一种缓慢的刺激后突触导电性 (EPSC). 这一发现揭示了TRPC1
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 第I组甲基酸盐受体 (mGluRs) 是参与神经可塑性和学习的G蛋白合受体.
- 在激活活动爆发后,I组mGluRs触发信号通路,包括脂酶C刺激和缓慢刺激后突触导电性 (EPSC).
- 介导mGluR1引起的缓慢EPSC的通道的分子身份仍然未知.
研究的目的:
- 为了确定负责mGluR1引起的缓慢刺激后突触导电性的阴离子通道.
- 研究TRPC1在大脑小纤维平行纤维-普尔金耶细胞突触中介突触传输中的作用.
主要方法:
- 在普金尼细胞中进行电生理学记录,以测量突触电流.
- 调查mGluR1和TRPC1.1之间的物理关联.
- 在异质表达系统中,mGluR1和TRPC1信号的功能复合.
主要成果:
- 该研究确定了TRPC1阴阳通道作为mGluR1-引起的缓慢EPSC的调解者.
- TRPC1在围突触区域表达,并在平行纤维-普尔金耶细胞突触处与mGluR1物理相关.
- 阻止TRPC1功能取消了mGluR1引起的缓慢EPSC,而不会影响快速的AMPA受体介导传播.
- 在异质系统中mGluR1和TRPC1的同时表达成功地重建了mGluR1引起的缓慢EPSC.
结论:
- TRPC1阴离子通道是mGluR1.1.激活的信号通路的重要组成部分.
- 这一发现阐明了mGluR1-介导的突触传输和神经可塑性的关键分子机制.
- 在涉及mGluR1功能障碍的疾病中,TRPC1是潜在的治疗点.
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