Ca 2+ /Calmodulin-Dependent Protein Kinase II Phosphorylation Regulates the Cardiac Ryanodine Receptor
Top Cited Papers
- 2 April 2004
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 94 (6) , e61-e70
- https://doi.org/10.1161/01.res.0000125626.33738.e2
Abstract
The cardiac ryanodine receptor (RyR2)/calcium release channel on the sarcoplasmic reticulum is required for muscle excitation-contraction coupling. Using site-directed mutagenesis, we identified the specific Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) phosphorylation site on recombinant RyR2, distinct from the site for protein kinase A (PKA) that mediates the “fight-or-flight” stress response. CaMKII phosphorylation increased RyR2 Ca 2+ sensitivity and open probability. CaMKII was activated at increased heart rates, which may contribute to enhanced Ca 2+ -induced Ca 2+ release. Moreover, rate-dependent CaMKII phosphorylation of RyR2 was defective in heart failure. CaMKII-mediated phosphorylation of RyR2 may contribute to the enhanced contractility observed at higher heart rates. The full text of this article is available online at http://circres.ahajournals.org .Keywords
This publication has 55 references indexed in Scilit:
- Altered function and regulation of cardiac ryanodine receptors in cardiac diseaseTrends in Biochemical Sciences, 2003
- Protein Phosphatases Decrease Sarcoplasmic Reticulum Calcium Content by Stimulating Calcium Release in Cardiac MyocytesThe Journal of Physiology, 2003
- Functional coupling of calcineurin and protein kinase A in mouse ventricular myocytesThe Journal of Physiology, 2002
- Dual Site Phospholamban Phosphorylation and Its Physiological Relevance in the HeartTrends in Cardiovascular Medicine, 2002
- FKBP12 Binding Modulates Ryanodine Receptor Channel GatingJournal of Biological Chemistry, 2001
- Phosphorylation with protein kinases modulates calcium loading of terminal cisternae of sarcoplasmic reticulum from skeletal muscleCell Calcium, 1995
- Phosphorylation Modulates the Function of the Calcium Release Channel of Sarcoplasmic Reticulum from Cardiac MuscleJournal of Biological Chemistry, 1995
- Enhancement of Ca2+ release channel activity by phosphorylation of the skeletal muscle ryanodine receptorFEBS Letters, 1993
- Phosphorylation of the porcine skeletal and cardiac muscle sarcoplasmic reticulum ryanodine receptorBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1993
- Phosphorylation of serine 2843 in ryanodine receptor-calcium release channel of skeletal muscle by cAMP-, cGMP- and CaM-dependent protein kinaseBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1993