Accumulation of Kv7.2 channels in putative ectopic transduction zones of mice nerve-end neuromas.
Accumulation of Kv7.2 channels in putative ectopic transduction zones of mice nerve-end neuromas.
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DOI：
10.1186/1744-8069-7-58
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发表时间：
2011-08-14
期刊：
影响因子：
3.3
通讯作者：
Lopez-García JA
中科院分区：
文献类型：
--
作者：
Roza C;Castillejo S;Lopez-García JA
由于M型电流在调节神经元兴奋性中的作用，其被提出作为治疗神经病理性疼痛的新策略。使用电生理学技术，我们先前表明，与瑞替加滨的Kv7通道的开放，阻断异位放电轴突切断的纤维，但不改变在完整的皮肤传入的转导。我们假设神经损伤后，传入纤维中Kv7通道的积累可能会增加M型电流，然后获得更重要的作用，在调节纤维兴奋性。在这项研究中，我们使用免疫组化方法来检查模式的Kv7.2通道的表达后，传入纤维轴突切断，并比较它们的模式的电压门控Na+通道（Nav），这是关键的生电元素在外周轴突已知的实验和人类神经瘤的积累。轴突切断引起的扩大和缩小的节点的Ranvier在近端的神经瘤连同一个戏剧性的脱髓鞘和损失的结构在其远端，其中赤裸裸的积累的Nav。此外，轴突切断还诱导与Nav通道共定位的Kv7.2的积累。虽然Nav通道对于动作电位的起始是强制性的（即负责异位放电的产生/传播），但轴突切断后Kv7.2通道的积累增加可能代表对轴突切断纤维中过度兴奋性的稳态补偿，为神经病变条件下M电流调节剂的外周作用打开窗口。
Modulation of M-type currents has been proposed as a new strategy for the treatment of neuropathic pain due to their role in regulating neuronal excitability. Using electrophysiological techniques we showed previously that the opening of Kv7 channels with retigabine, blocked ectopic discharges from axotomized fibers but did not alter transduction at intact skin afferents. We hypothesized that after nerve damage, accumulation of Kv7 channels in afferent fibers may increase M-type currents which then acquired a more important role at regulating fiber excitability. In this study, we used an immunohistochemical approach to examine patterns of expression of Kv7.2 channels in afferent fibers after axotomy and compared them to patterns of expression of voltage gated Na+ channels (Nav) which are key electrogenic elements in peripheral axons known to accumulate in experimental and human neuromas. Axotomy induced an enlargement and narrowing of the nodes of Ranvier at the proximal end of the neuroma together with a dramatic demyelination and loss of structure at its distal end in which naked accumulations of Nav were present. In addition, axotomy also induced accumulations of Kv7.2 that co-localized with those of Nav channels. Whilst Nav channels are mandatory for initiation of action potentials, (i.e. responsible for the generation/propagation of ectopic discharges) an increased accumulation of Kv7.2 channels after axotomy may represent a homeostatic compensation to over excitability in axotomized fibers, opening a window for a peripheral action of M-current modulators under conditions of neuropathy.
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影响因子：
4.8
作者：
Rivera-Arconada I;Roza C;Lopez-Garcia JA
通讯作者：
Lopez-Garcia JA
影响因子：
4
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Devor, M
通讯作者：
Devor, M
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7.4
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Henry, Michael A.;Freking, Angelique R.;Levinson, S. Rock
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2
作者：
Kretschmer, T;Nguyen, DH;Kline, DG
通讯作者：
Kline, DG
影响因子：
7.4
作者：
Taylor, Keri S.;Anastakis, Dimitri J.;Davis, Karen D.
通讯作者：
Davis, Karen D.