Open AccessReview Article : Phospholemman: A Novel Cardiac Stress Protein
Author(s) -
Cheung Joseph Y.,
Zhang XueQian,
Song Jianliang,
Gao Erhe,
Rabinowitz Joseph E.,
Chan Tung O.,
Wang JuFang
Publication year - 2010
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2010.00213.x
Subject(s) - phosphorylation , contractility , microbiology and biotechnology , myocyte , heart failure , chemistry , serca , cardiac muscle , intracellular , medicine , endocrinology , pharmacology , biology , atpase , biochemistry , enzyme
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