title: Intracellular Na⁺ and cardiac metabolism.
abstract: 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 Ca(2+) homeostasis. While elevated [Na(+)]i is thought to compensate for decreased Ca(2+) 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".
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Bay
authors.forename: Michael
authors.initials: M
authors.lastname: Kohlhaas
authors.forename: Christoph
authors.initials: C
authors.lastname: Maack
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004734:Energy Metabolism; D056966:Excitation Contraction Coupling; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006706:Homeostasis; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D020257:Ventricular Remodeling
chemical_list: D017382:Reactive Oxygen Species; D012964:Sodium; D002118:Calcium
keywords: Calcium; Heart failure; Mitochondria; Reactive oxygen species; Redox; Sodium