Intracellular Na+ and cardiac metabolism

In heart failure, alterations of excitation-contraction underlie contractile dysfunction. One important defect is an elevation of the intracellular Na+ concentration in cardiac myocytes ([Na+]i), which has an important impact on cytosolic and mitochondrial Ca2 + homeostasis. While elevated [Na+]i is thought to compensate for decreased Ca2 + load of the sarcoplasmic reticulum (SR), it yet negatively affects energy supply-and-demand matching and can even induce mitochondrial oxidative stress. Here, we review the mechanisms underlying these pathophysiological changes. The chain of events may constitute a vicious cycle of ion dysregulation, oxidative stress and energetic deficit, resembling characteristic cellular deficits that are considered key hallmarks of the failing heart. This article is part of a Special Issue entitled “Na+ Regulation in Cardiac Myocytes”.