Document Type

Article

Publication Date

8-1-2010

Comments

This article has been peer reviewed. It is the authors' final version prior to publication in Clinical and Translational Science, Volume 3, Issue 4, August 2010, Pages 189-196(8). The published version is available at . DOI: 10.1111/j.1752-8062.2010.00213.x. Copyright © Publishing Technology

Abstract

Phospholemman (PLM), a member of the FXYD family of regulators of ion transport, is a major sarcolemmal substrate for protein kinases A and C in cardiac and skeletal muscle. In the heart, PLM co-localizes and co-immunoprecipitates with Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and L-type Ca(2+) channel. Functionally, when phosphorylated at serine(68), PLM stimulates Na(+)-K(+)-ATPase but inhibits Na(+)/Ca(2+) exchanger in cardiac myocytes. In heterologous expression systems, PLM modulates the gating of cardiac L-type Ca(2+) channel. Therefore, PLM occupies a key modulatory role in intracellular Na(+) and Ca(2+) homeostasis and is intimately involved in regulation of excitation-contraction (EC) coupling. Genetic ablation of PLM results in a slight increase in baseline cardiac contractility and prolongation of action potential duration. When hearts are subjected to catecholamine stress, PLM minimizes the risks of arrhythmogenesis by reducing Na(+) overload and simultaneously preserves inotropy by inhibiting Na(+)/Ca(2+) exchanger. In heart failure, both expression and phosphorylation state of PLM are altered and may partly account for abnormalities in EC coupling. The unique role of PLM in regulation of Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and potentially L-type Ca(2+) channel in the heart, together with the changes in its expression and phosphorylation in heart failure, make PLM a rational and novel target for development of drugs in our armamentarium against heart failure. Clin Trans Sci 2010; Volume 3: 189-196.

Additional Files
figure1.jpg (37 kB)
Figure 1.
figure2.jpg (39 kB)
Figure 2.
figure3.jpg (77 kB)
Figure 3.
figure4.jpg (31 kB)
Figure 4.
figure5.jpg (46 kB)
Figure 5.

PubMed ID

20718822

Download

Included in

Cardiology Commons

Share

COinS