Fibroblast growth factor homologous factors serve as a molecular rheostat in tuning arrhythmogenic cardiac late sodium current.

ABSTRACT: Voltage-gated sodium (Nav1.5) channels support the genesis and brisk spatial propagation of action potentials in the heart. Disruption of Na_V1.5 inactivation results in a small persistent Na influx known as late Na current (I _Na,L), which has emerged as a common pathogenic mechanism in both congenital and acquired cardiac arrhythmogenic syndromes. Here, using low-noise multi-channel recordings in heterologous systems, LQTS3 patient-derived iPSCs cardiomyocytes, and mouse ventricular myocytes, we demonstrate that the intracellular fibroblast growth factor homologous factors (FHF1-4) tune pathogenic I _Na,L in an isoform-specific manner. This scheme suggests a complex orchestration of I _Na,L in cardiomyocytes that may contribute

SUBMITTER: Chakouri N 

PROVIDER: S-EPMC9161660 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature