title: Regulation of the cardiac sodium pump.
abstract: 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.
authors.affiliation: Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, College of Medicine Dentistry and Nursing, University of Dundee, Dundee, UK. w.fuller@dundee.ac.uk
authors.forename: W
authors.initials: W
authors.lastname: Fuller
authors.forename: L B
authors.initials: LB
authors.lastname: Tulloch
authors.forename: M J
authors.initials: MJ
authors.lastname: Shattock
authors.forename: S C
authors.initials: SC
authors.lastname: Calaghan
authors.forename: J
authors.initials: J
authors.lastname: Howie
authors.forename: K J
authors.initials: KJ
authors.lastname: Wypijewski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D016415:Sequence Alignment; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; C069141:phospholemman; D009569:Nitric Oxide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase