Calcium‐dependent Nedd4‐2 upregulation mediates degradation of the cardiac sodium channel Nav1.5: implications for heart failure

Reductions in voltage-gated sodium channel (Nav1.5) function/expression provide a slowed-conduction substrate for cardiac arrhythmias. Nedd4-2, which is activated by calcium, post-translationally modulates Nav1.5. We aim to investigate whether elevated intracellular calcium ([Ca2+ ]i ) reduces Nav1.5 through Nedd4-2 and its role in heart failure (HF).Using a combination of biochemical, electrophysiological, cellular and in vivo methods, we...