Potassium channel clustering: mechanisms shaping axonal excitability.

IF 4.2 3区 医学 Q2 NEUROSCIENCES
Frontiers in Cellular Neuroscience Pub Date : 2025-07-01 eCollection Date: 2025-01-01 DOI:10.3389/fncel.2025.1627517
Gabriel Escobedo, Matthew N Rasband
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引用次数: 0

Abstract

The precise clustering of ion channels at axon initial segments (AIS) and nodes of Ranvier is essential for axonal excitability and rapid action potential propagation. Among the axonal ion channels, voltage-gated potassium channels (Kv) and two-pore domain potassium (K2P) leak channels are key regulators of AIS and nodal excitability. Kv7 and Kv1 channels contribute to action potential threshold and repolarization at the AIS, and membrane repolarization in axons has historically been attributed to Kv channels. However, recent studies suggest that at nodes of Ranvier K2P channels, particularly TRAAK and TREK-1, play a dominant role in action potential repolarization. The interaction of Kv and K2P channels with diverse scaffolding proteins ensures their precise localization at AIS and nodes. Mislocalization or dysfunction of axonal Kv and K2P channels can cause epilepsy and neurodevelopmental disorders. This review explores the diversity of potassium channels and the mechanisms responsible for their clustering at AIS and nodes of Ranvier. Understanding these processes will be essential for therapeutic strategies aimed at treating diseases characterized by abnormal potassium channel expression, clustering, and function in neurons.

钾通道聚集:形成轴突兴奋性的机制。
轴突初始节段和Ranvier节点离子通道的精确聚集是轴突兴奋性和快速动作电位传播的必要条件。在轴突离子通道中,电压门控钾离子通道(Kv)和双孔域钾离子泄漏通道(K2P)是AIS和节点兴奋性的关键调控因子。Kv7和Kv1通道参与AIS的动作电位阈值和再极化,而轴突的膜再极化历来被认为是由Kv通道完成的。然而,最近的研究表明,Ranvier K2P通道的节点,特别是TRAAK和TREK-1,在动作电位复极化中起主导作用。Kv和K2P通道与多种支架蛋白的相互作用确保了它们在AIS和节点上的精确定位。轴突Kv和K2P通道定位错误或功能障碍可引起癫痫和神经发育障碍。本文综述了钾离子通道的多样性及其在AIS和Ranvier节点聚集的机制。了解这些过程对于治疗以异常钾通道表达、聚类和神经元功能为特征的疾病至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.90
自引率
3.80%
发文量
627
审稿时长
6-12 weeks
期刊介绍: Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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