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. (C) 2013 Elsevier Ltd. All rights reserved.