Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation.

ABSTRACT:

Background

Arginine (Arg) 14 deletion (R14del) in the calcium regulatory protein phospholamban (hPLN^R14del) has been identified as a disease-causing mutation in patients with an inherited cardiomyopathy. Mechanisms underlying the early arrhythmogenic phenotype that predisposes carriers of this mutation to sudden death with no apparent structural remodeling remain unclear.

Methods

To address this, we performed high spatiotemporal resolution optical mapping of intact hearts from adult knock-in mice harboring the human PLN^WT (wildtype [WT], n=12) or the heterozygous human PLN^R14del mutation (R14del, n=12) before and after ex vivo challenge with isoproterenol and rapid pacing.

Results

Adverse electrophysiological remodeling was evident in

SUBMITTER: Raad N 

PROVIDER: S-EPMC8456417 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature