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(Circulation Research. 2006;99:1290.)
© 2006 American Heart Association, Inc.

Editorials

Phospholemman and the Cardiac Sodium Pump

Protein Kinase C, Take a Bow

William Fuller, Michael J. Shattock

From the Institute for Cardiovascular Research (W.F.), Ninewells Hospital, University of Dundee, UK; and the Cardiovascular Division (M.J.S.), King’s College London, UK.

Correspondence to Dr William Fuller, University of Dundee, Vascular Diseases Unit, Institute for Cardiovascular Research, Ninewells Hospital & Medical School, Dundee DD1 9SY, United Kingdom. E-mail w.fuller@dundee.ac.uk

See related article, pages 1376–1383

Key Words: phospholemman • FXYD • protein kinase C • Na/K pump

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In excitable tissues, the activity of the plasmalemmal sodium/potassium ATPase (Na/K pump) is vital for the maintenance of normal electrical activity and ion gradients. In cardiac muscle, the transsarcolemmal sodium (Na) gradient established by the Na/K activity is essential not only for generating the rapid upstroke of the action potential but also for driving a number of ion exchange and transport processes that are crucial for normal cellular function, excitation contraction coupling, ion homeostasis and the control of cell volume. These Na-dependent membrane transporters include those responsible for the regulation of other ions (such as the sodium calcium exchanger (NCX), Na/H exchanger and Na-HCO₃ cotransporter), as well as those involved in the movement of substrates and amino acids.¹ By determining the set point for NCX, the Na/K pump controls the predominant mechanism of transmembrane calcium (Ca) flux, and hence indirectly controls intracellular Ca load and myocardial contractility. Interventions that influence either the activity of the Na/K pump, or indirectly the transmembrane sodium gradient, can therefore profoundly affect normal cardiac function.

Phospholemman, a type 1 transmembrane protein, is the predominant quantitative site of phosphorylation by protein kinase A (PKA) and protein kinase C (PKC) in cardiac sarcolemma.² PKA phosphorylates serine 68 and PKC phosphorylates serines 63 and 68 in phospholemman. For a long time following its cloning in 1991,³ the physiological role of phospholemman was unclear. Indeed, writing in this journal in 1998, researchers noted that "As a major target for hormone-stimulated phosphorylation in the heart, the physiological function of phospholemman . . . [Full Text of this Article]

Related Article:

Phospholemman Phosphorylation Mediates the Protein Kinase C–Dependent Effects on Na⁺/K⁺ Pump Function in Cardiac Myocytes

Fei Han, Julie Bossuyt, Sanda Despa, Amy L. Tucker, and Donald M. Bers
Circ. Res. 2006 99: 1376-1383. [Abstract] [Full Text] [PDF]

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				S. Bibert, S. Roy, D. Schaer, J.-D. Horisberger, and K. Geering Phosphorylation of Phospholemman (FXYD1) by Protein Kinases A and C Modulates Distinct Na,K-ATPase Isozymes J. Biol. Chem., January 4, 2008; 283(1): 476 - 486. [Abstract] [Full Text] [PDF]