title: Novel regulation of cardiac Na pump via phospholemman.
abstract: As the only quantitatively significant Na efflux pathway from cardiac cells, the Na/K ATPase (Na pump) is the primary regulator of intracellular Na. The transmembrane Na gradient it establishes is essential for normal electrical excitability, numerous coupled-transport processes and, as the driving force for Na/Ca exchange, thus setting cardiac Ca load and contractility. As Na influx varies with electrical excitation, heart rate and pathology, the dynamic regulation of Na efflux is essential. It is now widely recognized that phospholemman, a 72 amino acid accessory protein which forms part of the Na pump complex, is the key nexus linking cellular signaling to pump regulation. Phospholemman is the target of a variety of post-translational modifications (including phosphorylation, palmitoylation and glutathionation) and these can dynamically alter the activity of the Na pump. This review summarizes our current understanding of the multiple regulatory mechanisms that converge on phospholemman and govern NA pump activity in the heart. The corrected Fig. 4 is reproduced below. The publisher would like to apologize for any inconvenience caused. [corrected].
authors.affiliation: Cardiovascular Division, King's College London, The Rayne Institute, St Thomas' Hospital, London, UK. davor.pavlovic@kcl.ac.uk
authors.forename: Davor
authors.initials: D
authors.lastname: Pavlovic
authors.forename: William
authors.initials: W
authors.lastname: Fuller
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Shattock
mesh_terms: D000818:Animals; D006801:Humans; D054878:Lipoylation; D008565:Membrane Proteins / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; D019831:Sodium-Calcium Exchanger; C069141:phospholemman; D009569:Nitric Oxide; D011494:Protein Kinases
keywords: AR; ET(A); ET-1; FXYD-1; Heart; I-1; NCX; NO; NOS; Na/Ca exchanger; Na/K ATPase; PKA; PKC; PLB; PLM; PP-1; Phospholemman; Sodium pump; Sodium regulation; adrenergic receptor; endothelin 1; endothelin A receptor; inhibitor-1; nitric oxide; nitric oxide synthase; phosphatase-1; phospholamban; phospholemman; protein kinase A; protein kinase C