Kir2.1 dysfunction at the sarcolemma and the sarcoplasmic reticulum causes arrhythmias in a mouse model of Andersen-Tawil syndrome type 1.

ABSTRACT: Andersen-Tawil syndrome type 1 (ATS1) is associated with life-threatening arrhythmias of unknown mechanism. In this study, we generated and characterized a mouse model of ATS1 carrying the trafficking-deficient mutant Kir2.1^Δ314-315 channel. The mutant mouse recapitulates the electrophysiological phenotype of ATS1, with QT prolongation exacerbated by flecainide or isoproterenol, drug-induced QRS prolongation, increased vulnerability to reentrant arrhythmias and multifocal discharges resembling catecholaminergic polymorphic ventricular tachycardia (CPVT). Kir2.1^Δ314-315 cardiomyocytes display significantly reduced inward rectifier K⁺ and Na⁺ currents, depolarized resting membrane potential and prolonged action potentials. We show that, in wild-typ

SUBMITTER: Macias A 

PROVIDER: S-EPMC11358039 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature