7月26日,Nature Neuroscience发表了中国科学院上海生命科学研究院神经科学研究所舒友生研究组胡文钦等的研究论文 “钠通道亚型Nav1.6和Nav1.2在动作电位爆发和反向传播中的不同贡献”。该论文被选为封面故事。同期的“News and Views”还发表了斯坦福大学Dulla和Huguenard教授对该论文的重点介绍。
该研究论文试图回答神经科学领域的一个基本问题:动作电位的产生和传播的机制是什么?传统观点认为,动作电位在神经元轴突始段(AIS)爆发是由于该部位分布有高密度的Na+通道。在皮层锥体神经元的AIS上,近端和远端都存在高密度的Na+通道,但是动作电位却偏向性地在AIS远端爆发,这是什么原因?胡文钦等应用免疫荧光染色的方法发现高阈值的Nav1.2通道聚集在AIS的近端,而低阈值的Nav1.6通道聚集在AIS远端—对应于动作电位的爆发位点;应用电生理和计算机模拟等方法发现AIS远端的Nav1.6通道促进动作电位的爆发,近端的Nav1.2通道促进动作电位向胞体和树突的反向传播。这样,两种Na+通道亚型在动作电位的爆发和反向传播中的贡献截然不同。由于动作电位的爆发阈值决定了神经元的兴奋性,同时,反向传播的动作电位又是特定突触可塑性的基础;因此,AIS上Na+通道亚型是有效控制神经系统兴奋性和可塑性的重要靶向分子。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Neuroscience 12, 996 - 1002 (2009) 26 July 2009 | doi:10.1038/nn.2359
Distinct contributions of Nav1.6 and Nav1.2 in action potential initiation and backpropagation
Wenqin Hu1, Cuiping Tian1, Tun Li1, Mingpo Yang1, Han Hou1 & Yousheng Shu1
The distal end of the axon initial segment (AIS) is the preferred site for action potential initiation in cortical pyramidal neurons because of its high Na+ channel density. However, it is not clear why action potentials are not initiated at the proximal AIS, which has a similarly high Na+ channel density. We found that low-threshold Nav1.6 and high-threshold Nav1.2 channels preferentially accumulate at the distal and proximal AIS, respectively, and have distinct functions in action potential initiation and backpropagation. Patch-clamp recording from the axon cut end of pyramidal neurons in the rat prefrontal cortex revealed a high density of Na+ current and a progressive reduction in the half-activation voltage (up to 14 mV) with increasing distance from the soma at the AIS. Further modeling studies and simultaneous somatic and axonal recordings showed that distal Nav1.6 promotes action potential initiation, whereas proximal Nav1.2 promotes its backpropagation to the soma.
1 Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.