© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation
Clinic III of Internal Medicine, Laboratory of Muscle Research and Molecular Cardiology, University of Cologne, Cologne, Germany
robert.schwinger{at}medizin.uni-koeln.de
* Corresponding author. Priv.-Doz. Dr. med. Robert H.G. Schwinger, Klinik III für Innere Medizin der Universität zu Köln, Labor für Herzmuskelphysiologie und Molekulare Kardiologie, Joseph-Stelzmannstr. 9, 50924 Köln, Germany. Tel.: +49-221-478-3138; fax: +49-221-478-3746
The cardiac SR Ca2+-ATPase (SERCA2a) regulates intracellular Ca2+-handling and thus, plays a crucial role in initiating cardiac contraction and relaxation. SERCA2a may be modulated through its accessory phosphoprotein phospholamban or by direct phosphorylation through Ca2+/calmodulin dependent protein kinase II (CaMK II). As an inhibitory component phospholamban, in its dephosphorylated form, inhibits the Ca2+-dependent SERCA2a function, while protein kinase A dependent phosphorylation of the phospho-residues serine-16 or Ca2+/calmodulin-dependent phosphorylation of threonine-17 relieves this inhibition. Recent evidence suggests that direct phosphorylation at residue serine-38 in SERCA2a activates enzyme function and enhances Ca2+-reuptake into the sarcoplasmic reticulum (SR). These effects that are mediated through phosphorylation result in an overall increased SR Ca2+-load and enhanced contractility. In human heart failure patients, as well as animal models with induced heart failure, these modulations are altered and may result in an attenuated SR Ca2+-storage and modulated contractility. It is also believed that abnormalities in Ca2+-cycling are responsible for blunting the frequency potentiation of contractile force in the failing human heart. Advanced gene expression and modulatory approaches have focused on enhancing SERCA2a function via overexpressing SERCA2a under physiological and pathophysiological conditions to restore cardiac function, cardiac energetics and survival rate.
KEYWORDS Ca-pump; Calcium (cellular); Contractile function; SR (function)
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