title: Altered sarcoplasmic reticulum calcium cycling--targets for heart failure therapy.
abstract: Cardiac myocyte function is dependent on the synchronized movements of Ca(2+) into and out of the cell, as well as between the cytosol and sarcoplasmic reticulum. These movements determine cardiac rhythm and regulate excitation-contraction coupling. Ca(2+) cycling is mediated by a number of critical Ca(2+)-handling proteins and transporters, such as L-type Ca(2+) channels (LTCCs) and sodium/calcium exchangers in the sarcolemma, and sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a), ryanodine receptors, and cardiac phospholamban in the sarcoplasmic reticulum. The entry of Ca(2+) into the cytosol through LTCCs activates the release of Ca(2+) from the sarcoplasmic reticulum through ryanodine receptor channels and initiates myocyte contraction, whereas SERCA2a and cardiac phospholamban have a key role in sarcoplasmic reticulum Ca(2+) sequesteration and myocyte relaxation. Excitation-contraction coupling is regulated by phosphorylation of Ca(2+)-handling proteins. Abnormalities in sarcoplasmic reticulum Ca(2+) cycling are hallmarks of heart failure and contribute to the pathophysiology and progression of this disease. Correcting impaired intracellular Ca(2+) cycling is a promising new approach for the treatment of heart failure. Novel therapeutic strategies that enhance myocyte Ca(2+) homeostasis could prevent and reverse adverse cardiac remodeling and improve clinical outcomes in patients with heart failure.
authors.affiliation: Cardiovascular Research Center, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Changwon
authors.initials: C
authors.lastname: Kho
authors.forename: Ahyoung
authors.initials: A
authors.lastname: Lee
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D056966:Excitation Contraction Coupling; D006333:Heart Failure / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D002118:Calcium