Plantier Vanessa, Brocard Frédéric
Équipe P3M, Institut de Neurosciences de la Timone, UMR7289, Aix Marseille Université et Centre National de la Recherche Scientifique (CNRS), Marseille, France.
Med Sci (Paris). 2017 Jun-Jul;33(6-7):629-636. doi: 10.1051/medsci/20173306020. Epub 2017 Jul 19.
After a spinal cord injury (SCI), patients develop spasticity, a motor disorder characterized by hyperreflexia and stiffness of muscles. Spasticity results from alterations in motoneurons with an upregulation of their persistent sodium current (I ), simultaneously with a disinhibition caused by a reduction of expression of chloride (Cl) co-transporters KCC2. Until recently the origin of alterations was unknown. After reviewing pathophysiology of spasticity, the manuscript relates our recent work showing a tight relationship between the calpain-dependent proteolysis of voltage-gated sodium channels, the upregulation of I and spasticity following SCI. We also discuss KCC2 as a substrate of calpains which may contribute to the disinhibition of motoneurons below the lesion. This led us to consider the proteolytic cleavage of both sodium channels and KCC2 as the upstream mechanism contributing to the development of spasticity after SCI.
脊髓损伤（SCI）后，患者会出现痉挛，这是一种以反射亢进和肌肉僵硬为特征的运动障碍。痉挛是由运动神经元的改变引起的，其持续性钠电流（I ）上调，同时由于氯离子（Cl）共转运体KCC2表达减少导致去抑制作用。直到最近，这些改变的起源仍不清楚。在回顾了痉挛的病理生理学后，本文阐述了我们最近的研究工作，该研究表明电压门控钠通道的钙蛋白酶依赖性蛋白水解、I 的上调与脊髓损伤后的痉挛之间存在紧密联系。我们还讨论了KCC2作为钙蛋白酶的底物，它可能导致损伤平面以下运动神经元的去抑制。这使我们认为钠通道和KCC2的蛋白水解切割是脊髓损伤后导致痉挛发展的上游机制。
