Fading Sodium Channels in Failing Hearts

Abstract

See related article, pages 1146–1154 Heart failure (HF) affects over 5 million Americans with 550 000 new cases diagnosed each year. Despite advances in understanding and treatment the mortality rate remains extremely high with up to 50% of the patients dying suddenly.1 Ventricular arrhythmias are frequently the cause of sudden death in these heart failure patients. The mechanisms for these arrhythmias remain the focus of fervent research, but ion channel remodeling in the heart with prolongation of the action potential is one of the best documented changes in heart failure that lead to these fatal arrhythmias.2 Prolongation of the cardiac action potential can occur through a decrease in outward current or an increase in inward current during the plateau phase of the action potential. Reduction in outwardly conducting potassium channels during heart failure has been well documented.2,3 The role of the inwardly conducting cardiac sodium channel (NaV1.5) in sudden death in heart failure patients is much less clear. In this issue of Circulation Research , Shang et al4 report a novel contribution of altered gene transcription in failing hearts to the expression of potentially arrhythmogenic dysfunctional sodium channels expressed in the heart. During excitation, opening of the cardiac sodium channel produces a large and rapid inward current that underlies membrane depolarization and conduction of electrical impulses in the heart. The precise timing of ion channel opening and closing can be altered under pathological conditions or during drug …