Regulation of Intracellular and Mitochondrial Sodium in Health and Disease

• Published in: Circulation research 2009-02, Vol.104 (3), p.292-303
• Main Authors: Murphy, Elizabeth, Eisner, David A
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiology. Vascular system; Errors of metabolism; Fundamental and applied biological sciences. Psychology; Heart; Heart Diseases - metabolism; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Mitochondria - metabolism; Sodium - metabolism; Sodium Channels - metabolism; Sodium-Hydrogen Exchangers - metabolism; Vertebrates: cardiovascular system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.108.189050

The transmembrane sodium gradient is essential for both excitability of the cardiac cell and the regulation of the cytoplasmic concentrations of Ca and protons. In addition, movements of Na across the mitochondrial membrane affect matrix protons and calcium. In the first part of the review, we discuss the most important pathways responsible for sarcolemmal and mitochondrial sodium movements. The bulk of the review considers the changes of intracellular Na concentration ([Na]i) that occur in disease, specifically, ischemia, reperfusion, and heart failure. We review evidence implicating the increase of intracellular sodium to either increased influx of sodium (via either sodium channels or sodium/hydrogen exchange) or, alternatively, to decreased efflux on the Na/K pump. Although much has been learned about sodium regulation in the heart, there are still many unanswered questions, particularly concerning mitochondrial Na regulation.