Channelopathy: Arrhythmia, Cardiomyopathy, Epilepsy and Beyond

Overview

Journal Philos Trans R Soc Lond B Biol Sci

Specialty Biology

Date 2023 May 1

PMID 37122208

Authors

Carol Ann Remme

Affiliations

Soon will be listed here.

Abstract

Influx of sodium ions through voltage-gated sodium channels in cardiomyocytes is essential for proper electrical conduction within the heart. Both acquired conditions associated with sodium channel dysfunction (myocardial ischaemia, heart failure) as well as inherited disorders secondary to mutations in the gene encoding for the cardiac sodium channel Nav1.5 are associated with life-threatening arrhythmias. Research in the last decade has uncovered the complex nature of Nav1.5 distribution, function, in particular within distinct subcellular subdomains of cardiomyocytes. Nav1.5-based channels furthermore display previously unrecognized non-electrogenic actions and may impact on cardiac structural integrity, leading to cardiomyopathy. Moreover, and Nav1.5 are expressed in cell types other than cardiomyocytes as well as various extracardiac tissues, where their functional role in, e.g. epilepsy, gastrointestinal motility, cancer and the innate immune response is increasingly investigated and recognized. This review provides an overview of these novel insights and how they deepen our mechanistic knowledge on channelopathies and Nav1.5 (dys)function. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

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