Markedly reduced axonal potassium channel expression in human sporadic amyotrophic lateral sclerosis: An immunohistochemical study
Markedly reduced axonal potassium channel expression in human sporadic amyotrophic lateral sclerosis: An immunohistochemical study
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DOI：
10.1016/j.expneurol.2011.08.015
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发表时间：
2011-12-01
影响因子：
5.3
通讯作者：
Kuwabara, Satoshi
中科院分区：
文献类型：
--
作者：
Shibuya, Kazumoto;Misawa, Sonoko;Kuwabara, Satoshi
肌束是肌萎缩侧索硬化症（ALS）的特征性特征，表明运动轴突的兴奋性异常增加。先前的神经兴奋性研究表明，ALS患者的轴突钾电流减少，可能导致过度兴奋，从而产生肌束震颤。为了阐明ALS运动轴突中轴突离子通道表达的变化，我们对5例散发性ALS尸检病例的C7和L5腹根/背根中的钾和钠通道进行了免疫组化。与对照组相比，所有ALS患者的前根钾通道（Kv1.2）的免疫反应性明显降低，但在背根的正常。结钠通道表达在ALS患者和对照组中没有显著差异。我们的研究结果表明，在ALS患者的运动轴突中，轴突钾通道的表达显著降低，并提供了神经病理学和生物学基础，为运动轴突的抑制性钾电流降低。轴索过度兴奋可导致肌束震颤的产生，并可能促进ALS中运动神经元的死亡。(C)2011 Elsevier Inc. All rights reserved.
Fasciculations are characteristic features of amyotrophic lateral sclerosis (ALS), suggesting abnormally increased excitability of motor axons. Previous nerve excitability studies have shown reduced axonal potassium currents in ALS patients that may contribute to the hyperexcitability and thereby generation of fasciculations. To clarify changes in axonal ion channel expression in motor axons of ALS, we performed immunohistochemistry of potassium and sodium channels in the C7 and L5 ventral/dorsal roots obtained from five autopsy cases of sporadic ALS. Compared to controls, the immunoreactivity of potassium channels (Kv1.2) was markedly reduced in the ventral roots, but normal in the dorsal roots of all the ALS patients. Nodal sodium channel expression was not significantly different in ALS patients and control subjects. Our results show prominently reduced expression of axonal potassium channels, and provide the neuropathological and biological basis for decreased accommodative potassium currents in motor axons of ALS patients. The axonal hyperexcitability would lead to generation of fasciculations, and possibly enhances motor neuron death in ALS. (C) 2011 Elsevier Inc. All rights reserved.