Na+-dependent SR Ca2+ overload induces arrhythmogenic events in mouse cardiomyocytes with a human CPVT mutation

摘要

Aims Mutations in the cardiac ryanodine receptor Ca2+ release channel, RyR2, underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited life-threatening arrhythmia. CPVT is triggered by spontaneous RyR2-mediated sarcoplasmic reticulum (SR) Ca2+ release in response to SR Ca2+ overload during β-adrenergic stimulation. However, whether elevated SR Ca2+ content—in the absence of protein kinase A activation—affects RyR2 function and arrhythmogenesis in CPVT remains elusive.