Arrhythmias precede cardiomyopathy and remodeling of Ca2+ handling proteins in a novel model of long QT syndrome

•A new SCN5A long QT syndrome mouse model recapitulates the human clinical phenotype.•The pathological late Na+ current contributes to the cardiac electrical dysfunctions.•The arrhythmias precede structural defects and key Ca2+ handling proteins remodeling.•Ranolazine, a late Na+ current inhibitor, reduces action potential and QT prolongation.