Ca2+/Calmodulin-Dependent Protein Kinase II Phosphorylation Regulates the Cardiac Ryanodine Receptor

XHT Wehrens, SE Lehnart, SR Reiken… - Circulation …, 2004 - Am Heart Assoc
Circulation research, 2004Am Heart Assoc
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 Ca2+/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 Ca2+ sensitivity and open probability. CaMKII was activated at increased …
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 Ca2+/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 Ca2+ sensitivity and open probability. CaMKII was activated at increased heart rates, which may contribute to enhanced Ca2+-induced Ca2+ 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.
Am Heart Assoc