7月26日,Nature Neuroscience發(fā)表了中國科學(xué)院上海生命科學(xué)研究院神經(jīng)科學(xué)研究所舒友生研究組胡文欽等的研究論文 “鈉通道亞型Nav1.6和Nav1.2在動(dòng)作電位爆發(fā)和反向傳播中的不同貢獻(xiàn)”,。該論文被選為封面故事。同期的“News and Views”還發(fā)表了斯坦福大學(xué)Dulla和Huguenard教授對該論文的重點(diǎn)介紹,。
該研究論文試圖回答神經(jīng)科學(xué)領(lǐng)域的一個(gè)基本問題:動(dòng)作電位的產(chǎn)生和傳播的機(jī)制是什么,?傳統(tǒng)觀點(diǎn)認(rèn)為,動(dòng)作電位在神經(jīng)元軸突始段(AIS)爆發(fā)是由于該部位分布有高密度的Na+通道,。在皮層錐體神經(jīng)元的AIS上,,近端和遠(yuǎn)端都存在高密度的Na+通道,但是動(dòng)作電位卻偏向性地在AIS遠(yuǎn)端爆發(fā),,這是什么原因,?胡文欽等應(yīng)用免疫熒光染色的方法發(fā)現(xiàn)高閾值的Nav1.2通道聚集在AIS的近端,而低閾值的Nav1.6通道聚集在AIS遠(yuǎn)端—對應(yīng)于動(dòng)作電位的爆發(fā)位點(diǎn),;應(yīng)用電生理和計(jì)算機(jī)模擬等方法發(fā)現(xiàn)AIS遠(yuǎn)端的Nav1.6通道促進(jìn)動(dòng)作電位的爆發(fā),,近端的Nav1.2通道促進(jìn)動(dòng)作電位向胞體和樹突的反向傳播,。這樣,,兩種Na+通道亞型在動(dòng)作電位的爆發(fā)和反向傳播中的貢獻(xiàn)截然不同,。由于動(dòng)作電位的爆發(fā)閾值決定了神經(jīng)元的興奮性,同時(shí),,反向傳播的動(dòng)作電位又是特定突觸可塑性的基礎(chǔ),;因此,,AIS上Na+通道亞型是有效控制神經(jīng)系統(tǒng)興奮性和可塑性的重要靶向分子,。(生物谷Bioon.com)
生物谷推薦原始出處:
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.