Neuronal Na(+) Channels Are Integral Components of Pro-arrhythmic Na(+)/Ca(2+) Signaling Nanodomain That Promotes Cardiac Arrhythmias During β-adrenergic Stimulation

Background—Cardiac arrhythmias are a leading cause of death in the US. Vast majority of these arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT) are associated with increased levels of circulating catecholamines and involve abnormal impulse formation secondary to aberrant Ca2+ and Na+ handling. However, the mechanistic link between β-AR stimulation and the subcellular/molecular arrhythmogenic trigger(s) remains elusive.