神经元中的持续钠电流:潜在机制和药理阻断剂。

IF 2.9 4区 医学 Q2 PHYSIOLOGY
Peter Müller, Andreas Draguhn, Alexei V Egorov
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引用次数: 0

摘要

持续钠电流(INaP)是神经元兴奋性的一个重要活动依赖性调节器。它参与了多种生理和病理过程,包括起搏、感觉电位延长、神经元损伤、慢性疼痛以及癫痫和肌萎缩性脊髓侧索硬化症等疾病。尽管 INaP 非常重要,但人们对其分子基础和调控机制都了解得不够。尤为重要的是,人们对分析 INaP 功能和开发新治疗策略的药理学工具有了扎实的了解,并达成了广泛的共识。然而,有关 INaP 的文献资料参差不齐,不同研究采用的定义和方法也不尽相同。为了解决这些问题,我们对目前有关 INaP 的知识进行了系统回顾,重点是这种电流在中枢神经系统中的机制和效应。我们概述了最广泛使用的 INaP 阻断剂的特异性和功效:胺碘酮、大麻二酚、卡马西平、仙诺巴马特、艾司卡西平、乙琥胺、加巴喷丁、GS967、拉科萨胺、拉莫三嗪、利多卡因、NBI-921352、奥卡西平、苯妥英钠、PRAX-562、丙泊酚、雷诺嗪、利鲁唑、鲁非那胺、托吡酯、丙戊酸和唑尼沙胺。我们的结论是,这些药物的药理作用和可用信息存在很大差异。目前,GS967 和利鲁唑可被视为真正的 INaP 阻滞剂,而苯妥英和拉科酰胺则是仅对钠电流的缓慢失活成分起作用的阻滞剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers.

Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers.

Persistent sodium current (INaP) is an important activity-dependent regulator of neuronal excitability. It is involved in a variety of physiological and pathological processes, including pacemaking, prolongation of sensory potentials, neuronal injury, chronic pain and diseases such as epilepsy and amyotrophic lateral sclerosis. Despite its importance, neither the molecular basis nor the regulation of INaP are sufficiently understood. Of particular significance is a solid knowledge and widely accepted consensus about pharmacological tools for analysing the function of INaP and for developing new therapeutic strategies. However, the literature on INaP is heterogeneous, with varying definitions and methodologies used across studies. To address these issues, we provide a systematic review of the current state of knowledge on INaP, with focus on mechanisms and effects of this current in the central nervous system. We provide an overview of the specificity and efficacy of the most widely used INaP blockers: amiodarone, cannabidiol, carbamazepine, cenobamate, eslicarbazepine, ethosuximide, gabapentin, GS967, lacosamide, lamotrigine, lidocaine, NBI-921352, oxcarbazepine, phenytoine, PRAX-562, propofol, ranolazine, riluzole, rufinamide, topiramate, valproaic acid and zonisamide. We conclude that there is strong variance in the pharmacological effects of these drugs, and in the available information. At present, GS967 and riluzole can be regarded bona fide INaP blockers, while phenytoin and lacosamide are blockers that only act on the slowly inactivating component of sodium currents.

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来源期刊
CiteScore
8.80
自引率
2.20%
发文量
121
审稿时长
4-8 weeks
期刊介绍: Pflügers Archiv European Journal of Physiology publishes those results of original research that are seen as advancing the physiological sciences, especially those providing mechanistic insights into physiological functions at the molecular and cellular level, and clearly conveying a physiological message. Submissions are encouraged that deal with the evaluation of molecular and cellular mechanisms of disease, ideally resulting in translational research. Purely descriptive papers covering applied physiology or clinical papers will be excluded. Papers on methodological topics will be considered if they contribute to the development of novel tools for further investigation of (patho)physiological mechanisms.
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