Molecular and Functional Relevance of Na_V1.8-Induced Atrial Arrhythmogenic Triggers in a Human SCN10A Knock-Out Stem Cell Model.

ABSTRACT: In heart failure and atrial fibrillation, a persistent Na⁺ current (I_NaL) exerts detrimental effects on cellular electrophysiology and can induce arrhythmias. We have recently shown that Na_V1.8 contributes to arrhythmogenesis by inducing a I_NaL. Genome-wide association studies indicate that mutations in the SCN10A gene (Na_V1.8) are associated with increased risk for arrhythmias, Brugada syndrome, and sudden cardiac death. However, the mediation of these Na_V1.8-related effects, whether through cardiac ganglia or cardiomyocytes, is still a subject of controversial discussion. We used CRISPR/Cas9 technology to generate homozygous atrial SCN10A-KO-iPSC-CMs. Ruptured-patch whole-cell patch-clamp was used to measure

SUBMITTER: Hartmann N 

PROVIDER: S-EPMC10299073 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature