Hu Wenqin, Tian Cuiping, Li Tun, Yang Mingpo, Hou Han, Shu Yousheng
Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Nat Neurosci. 2009 Aug;12(8):996-1002. doi: 10.1038/nn.2359. Epub 2009 Jul 26.
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 Na(v)1.6 and high-threshold Na(v)1.2 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 Na(v)1.6 promotes action potential initiation, whereas proximal Na(v)1.2 promotes its backpropagation to the soma.
轴突起始段（AIS）的远端是皮质锥体神经元中动作电位起始的首选部位，因为其具有高钠通道密度。然而，尚不清楚为什么动作电位不在近端AIS起始，近端AIS也具有类似的高钠通道密度。我们发现，低阈值的Na(v)1.6通道和高阈值的Na(v)1.2通道分别优先聚集在AIS的远端和近端，并且在动作电位起始和回传中具有不同的功能。对大鼠前额叶皮质锥体神经元轴突切断端进行膜片钳记录，结果显示在AIS处，钠电流密度很高，并且随着距胞体距离的增加，半激活电压逐渐降低（高达14mV）。进一步的建模研究以及同时进行的体细胞和轴突记录表明，远端的Na(v)1.6促进动作电位的起始，而近端的Na(v)1.2则促进其向胞体的回传。
