Regulation of the cardiac sodium pump

• Published in: Cellular and molecular life sciences : CMLS Vol. 70; no. 8; pp. 1357 - 1380
• Main Authors: Fuller, W., Tulloch, L. B., Shattock, M. J., Calaghan, S. C., Howie, J., Wypijewski, K. J.
• Format: Journal Article
• Language: English
• Published: Basel SP Birkhäuser Verlag Basel 01.04.2013; Springer Nature B.V
• Subjects: Active transport; Amino Acid Sequence; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cardiac muscle; Cell Biology; Cell surface; Cellular biology; Cyclic AMP-Dependent Protein Kinases - metabolism; Gene expression; Heart; Humans; Ion exchange; Life Sciences; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Models, Molecular; Molecular biology; Molecular Sequence Data; Muscle contraction; Myocardium - metabolism; Myocytes; Na+/K+-exchanging ATPase; Nitric Oxide - metabolism; Palmitoylation; Phospholemman; Phosphoproteins - chemistry; Phosphoproteins - metabolism; Phosphorylation; Post-translation; Protein Kinase C - metabolism; Protein Processing, Post-Translational; Review; Sequence Alignment; Sodium; Sodium-Potassium-Exchanging ATPase - chemistry; Sodium-Potassium-Exchanging ATPase - metabolism; Transport processes; Heart; Protein kinase A; Phospholemman; Protein kinase C; Palmitoylation; Ion transport; Intracellular sodium; Sodium pump; FXYD
• ISSN: 1420-682X; 1420-9071; 1420-9071
• DOI: 10.1007/s00018-012-1134-y

In cardiac muscle, the sarcolemmal sodium/potassium ATPase is the principal quantitative means of active transport at the myocyte cell surface, and its activity is essential for maintaining the trans-sarcolemmal sodium gradient that drives ion exchange and transport processes that are critical for cardiac function. The 72-residue phosphoprotein phospholemman regulates the sodium pump in the heart: unphosphorylated phospholemman inhibits the pump, and phospholemman phosphorylation increases pump activity. Phospholemman is subject to a remarkable plethora of post-translational modifications for such a small protein: the combination of three phosphorylation sites, two palmitoylation sites, and one glutathionylation site means that phospholemman integrates multiple signaling events to control the cardiac sodium pump. Since misregulation of cytosolic sodium contributes to contractile and metabolic dysfunction during cardiac failure, a complete understanding of the mechanisms that control the cardiac sodium pump is vital. This review explores our current understanding of these mechanisms.