Cytoskeletal disarray increases arrhythmogenic vulnerability during sympathetic stimulation in a model of hypertrophic cardiomyopathy.

ABSTRACT: Familial hypertrophic cardiomyopathy (FHC) patients are advised to avoid strenuous exercise due to increased risk of arrhythmias. Mice expressing the human FHC-causing mutation R403Q in the myosin heavy chain gene (MYH6) recapitulate the human phenotype, including cytoskeletal disarray and increased arrhythmia susceptibility. Following in vivo administration of isoproterenol, mutant mice exhibited tachyarrhythmias, poor recovery and fatigue. Arrhythmias were attenuated with the β-blocker atenolol and protein kinase A inhibitor PKI. Mutant cardiac myocytes had significantly prolonged action potentials and triggered automaticity due to reduced repolarization reserve and connexin 43 expression. Isoproterenol shortened cycle length, and escalated electrical instability. Surprisingly isoprotere

SUBMITTER: Cserne Szappanos H 

PROVIDER: S-EPMC10338442 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature