Alterations of action potentials and the localization of Nav1.6 sodium channels in spared axons after hemisection injury of the spinal cord in adult rats
Alterations of action potentials and the localization of Nav1.6 sodium channels in spared axons after hemisection injury of the spinal cord in adult rats
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DOI：
10.1152/jn.00810.2010
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发表时间：
2011-03-01
影响因子：
2.5
通讯作者：
Arvanian, Victor L.
中科院分区：
文献类型：
--
作者：
Hunanyan, Arsen S.;Alessi, Valentina;Arvanian, Victor L.
湖南岩 AS，阿莱西 V，帕特尔 S，皮尔斯 DD，马修斯 G，阿瓦尼安 VL。成年大鼠脊髓半切损伤后幸存轴突中动作电位的变化和 Nav1.6 钠通道的定位。 《神经生理学杂志》105：1033-1044，2011 年。首次发表于 2010 年 12 月 22 日； doi: 10.1152/jn.00810.2010.-之前，我们报道了成年大鼠脊髓慢性半切 (HX) 对侧幸存轴突的传播明显减少。为了检查导致这种传输减弱的细胞和分子机制，我们在体内记录了深度麻醉的成年大鼠腰椎外侧白质轴突的细胞内情况，并测量了动作电位（AP）通过红核脊髓/网状脊髓束（RST/RtST）轴突在T10时与慢性HX对侧的传播。我们发现这些轴突的兴奋性降低，表现为触发 AP 的流变碱增加以及 AP 传播通过损伤水平的潜伏期更长，而轴突静息膜电位和输入电阻没有显着差异。这些电生理变化与 Nav1.6 钠通道沿轴突的空间定位改变有关：损伤对侧的轴突子集表现出 Nav1.6 通道的弥漫性定位（> 10 μ m 扩散），这是脱髓鞘轴突的模式特征（Craner MJ、Newcombe J、Black JA、Hartle C、Cuzner ML、Waxman SG。Proc Natl Acad Sci USA 101： 8168-8173, 2004b)。电子显微镜观察到的超微结构变化证实了这一结果，其中发现慢性 HX 对侧的大口径脱髓鞘 RST 轴突数量增加。因此，流变碱的增加、Nav1.6钠通道分布的病理变化以及对侧RST轴突的脱髓鞘可能是HX后传导长期下降的原因，因此可能为改善不完全脊髓损伤后功能的策略提供新的靶标。
Hunanyan AS, Alessi V, Patel S, Pearse DD, Matthews G, Arvanian VL. Alterations of action potentials and the localization of Nav1.6 sodium channels in spared axons after hemisection injury of the spinal cord in adult rats. J Neurophysiol 105: 1033-1044, 2011. First published December 22, 2010; doi: 10.1152/jn.00810.2010.-Previously, we reported a pronounced reduction in transmission through surviving axons contralateral to chronic hemisection (HX) of adult rat spinal cord. To examine the cellular and molecular mechanisms responsible for this diminished transmission, we recorded intracellularly from lumbar lateral white matter axons in deeply anesthetized adult rats in vivo and measured the propagation of action potentials (APs) through rubrospinal/reticulospinal tract (RST/RtST) axons contralateral to chronic HX at T10. We found decreased excitability in these axons, manifested by an increased rheobase to trigger APs and longer latency for AP propagation passing the injury level, without significant differences in axonal resting membrane potential and input resistance. These electrophysiological changes were associated with altered spatial localization of Nav1.6 sodium channels along axons: a subset of axons contralateral to the injury exhibited a diffuse localization (> 10 mu m spread) of Nav1.6 channels, a pattern characteristic of demyelinated axons (Craner MJ, Newcombe J, Black JA, Hartle C, Cuzner ML, Waxman SG. Proc Natl Acad Sci USA 101: 8168-8173, 2004b). This result was substantiated by ultrastructural changes seen with electron microscopy, in which an increased number of large-caliber, demyelinated RST axons were found contralateral to the chronic HX. Therefore, an increased rheobase, pathological changes in the distribution of Nav1.6 sodium channels, and the demyelination of contralateral RST axons are likely responsible for their decreased conduction chronically after HX and thus may provide novel targets for strategies to improve function following incomplete spinal cord injury.