Redistribution of Kv2.1 ion channels on spinal motoneurons following peripheral nerve injury.

Redistribution of Kv2.1 ion channels on spinal motoneurons following peripheral nerve injury.
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DOI:
10.1016/j.brainres.2013.12.012
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发表时间:
2014-02-14
期刊:
影响因子:
2.9
通讯作者:
Fyffe, Robert. E. W.
Fyffe, Robert. E. W.
中科院分区:
医学3区
文献类型:
--
作者:
Romer, Shannon H.;Dominguez, Kathleen M.;Gelpi, Marc W.;Deardorff, Adam S.;Tracy, Robert C.;Fyffe, Robert. E. W.

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周围神经损伤的病理生理反应包括脊髓神经元的活性、固有膜特性和兴奋性的改变。α-运动神经元的内在兴奋性部分受膜结合离子通道的表达、调节和分布控制。离子通道,如Kv2.1和SK,分别是延迟整流钾电流和后超极化的基础,位于特定的突触后位点的高密度簇。以前的工作表明,Kv2.1通道的聚集和动力学是由各种刺激,包括缺血,缺氧,神经调节剂的作用和增加的活动。通过通道去磷酸化进行调节,导致通道动力学的去簇和改变,从而使活性正常化。在这里,我们证明使用免疫组化,周围神经损伤也足以改变运动神经元上的Kv2.1通道的表面分布。通道定位的动态变化包括簇大小的快速进行性下降,在轴突切断后立即开始,在一周内达到最大值。通过神经再生,Kv2.1集群的组织和大小无法完全恢复。然而,在没有神经再支配的情况下,Kv2.1簇大小完全恢复。此外,单侧周围神经损伤引起平行的,但较小的影响,双边。这些结果表明,轴突损伤后运动神经元Kv2.1膜分布的稳态调节在很大程度上独立于轴突再神经支配。
Pathophysiological responses to peripheral nerve injury include alterations in the activity, intrinsic membrane properties and excitability of spinal neurons. The intrinsic excitability of α-motoneurons is controlled in part by the expression, regulation, and distribution of membrane-bound ion channels. Ion channels, such as Kv2.1 and SK, which underlie delayed rectifier potassium currents and afterhyperpolarization respectively, are localized in high-density clusters at specific postsynaptic sites. Previous work has indicated that Kv2.1 channel clustering and kinetics are regulated by a variety of stimuli including ischemia, hypoxia, neuromodulator action and increased activity. Regulation occurs via channel dephosphorylation leading to both declustering and alterations in channel kinetics, thus normalizing activity. Here we demonstrate using immunohistochemistry that peripheral nerve injury is also sufficient to alter the surface distribution of Kv2.1 channels on motoneurons. The dynamic changes in channel localization include a rapid progressive decline in cluster size, beginning immediately after axotomy, reaching maximum within one week. With reinnervation, the organization and size of Kv2.1 clusters do not fully recover. However, in the absence of reinnervation Kv2.1 cluster sizes fully recover. Moreover, unilateral peripheral nerve injury evokes parallel, but smaller, effects bilaterally. These results suggest that homeostatic regulation of motoneuron Kv2.1 membrane distribution after axon injury is largely independent of axon reinnervation.
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