Retigabine reduces the excitability of unmyelinated peripheral human axons
Retigabine reduces the excitability of unmyelinated peripheral human axons
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DOI：
10.1016/j.neuropharm.2008.04.006
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发表时间：
2008-06-01
影响因子：
4.7
通讯作者：
Grafe, P.
中科院分区：
文献类型：
--
作者：
Lang, P. M.;Fleckenstein, J.;Grafe, P.
在神经性疼痛中，膜K+电导的增强可能会降低初级传入伤害感觉神经元的异常兴奋性。研究表明，雷沙滨是一种新型抗惊厥药，可激活外周髓系轴突轴突/节膜上的Kv7 （KCNQ/M）通道。在本研究中，我们测试了雷吉滨对离体人腓肠神经束c型神经纤维兴奋性参数的影响。应用瑞加滨（3 ~ 10 μ M）可使膜阈值升高。这种效应在去极化轴突中明显，在超极化轴突中较小。这一发现表明，雷吉滨产生的膜超极化受K+平衡电位的限制。雷吉gabine诱导的兴奋性降低伴随着峰后恢复周期的改变。最值得注意的是在动作电位短爆发后的250-400 ms出现晚期亚兴奋性。在XE991 （10 μ M）存在下，瑞加滨的所有作用被阻断。数据显示，Kv7通道存在于无髓鞘神经的轴突上，包括人类的外周神经纤维。雷加滨激活这些通道可能会减少神经性疼痛中动作电位的异位产生。(c) 2008 Elsevier Ltd.版权所有。
Enhancement of membrane K+ conductance may reduce the abnormal excitability of primary afferent nociceptive neurons in neuropathic pain. It has been shown that retigabine, a novel anticonvulsant, activates Kv7 (KCNQ/M) channels in the axonal/nodal membrane of peripheral myelinated axons. In this study, we have tested the effects of retigabine on excitability parameters of C-type nerve fibers in isolated fascicles of human sural nerve. Application of retigabine (3-10 mu M) produced an increase in membrane threshold. This effect was pronounced in depolarized axons and small in hyperpolarized axons. This finding indicates that retigabine produces a membrane hyperpolarization which is limited by the K+ equilibrium potential. The retigabine-induced reduction in excitability was accompanied by modifications of the post-spike recovery cycle. Most notable is the development of a late subexcitability at 250-400 ms following a short burst of action potentials. All effects of retigabine were blocked in the presence of XE991 (10 mu M). The data show that Kv7 channels are present on axons of unmyelinated, including nociceptive, peripheral human nerve fibers. It is likely that activation of these channels by retigabine may reduce the ectopic generation of action potentials in neuropathic pain. (c) 2008 Elsevier Ltd. All rights reserved.