Neuronal Na⁺ Channels Are Integral Components of Pro-arrhythmic Na⁺/Ca²⁺ Signaling Nanodomain That Promotes Cardiac Arrhythmias During β-adrenergic Stimulation.

ABSTRACT:

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.

Methods and results

We performed functional and structural studies to assess Ca²⁺ and Na⁺ signaling in ventricular myocyte as well as surface electrocardiograms in mouse models of cardiac calsequestrin (CASQ2)-associated CPVT. We demonstrate that a subpopulation of Na⁺ chan

SUBMITTER: Radwanski PB 

PROVIDER: S-EPMC5065245 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature