{"title":"Potassium channel clustering: mechanisms shaping axonal excitability.","authors":"Gabriel Escobedo, Matthew N Rasband","doi":"10.3389/fncel.2025.1627517","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1627517"},"PeriodicalIF":4.2000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259577/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cellular Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fncel.2025.1627517","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
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.
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.