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(Circulation Research. 2008;103:e10.)
© 2008 American Heart Association, Inc.

Letters to the Editor

Ca²⁺-Calmodulin–Dependent Protein Kinase Phosphorylation of Ryanodine Receptor May Contribute to the β-Adrenergic Regulation of Myocardial Contractility Independently of Increases in Heart Rate

Alicia Mattiazzi, Leticia Vittone, Cecilia Mundiña-Weilenmann

Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina, E-mail ramattia@atlas.med.unlp.edu.ar

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

In a recent article, MacDonnell et al¹ reported that protein kinase A (PKA) phosphorylation of ryanodine receptor (RyR2) (the Ca²⁺ release channel of the sarcoplasmic reticulum [SR]) at Ser2808/09 site does not have a major role in the sympathetic nervous system (SNS) regulation of cardiac function. This conclusion was based on comparing the effect of isoproterenol on ventricular performance, in vivo, in isolated hearts and myocytes, in wild-type mice and in a genetically modified mouse in which Ser2808 of RyR2 was replaced by alanine (S2808A) to prevent PKA-mediated phosphorylation at this site. Isoproterenol produced an increase in cardiac function both in vivo and in isolated hearts, as well as an enhancement in the L-type Ca²⁺ current (I_CaL), the amplitude of the Ca²⁺ transient and the excitation–contraction coupling (ECC) gain in isolated myocytes, which were not significantly different between wild-type and S2808A mice.

We have previously demonstrated the lack of functionality of the PKA-dependent phosphorylation of RyR2 at Ser2808/09.² In perfused rat hearts, we showed that the isoproterenol-induced phosphorylation of RyR2 was associated with an enhancement of the [³H]-ryanodine binding and the velocity of fast Ca²⁺ release in SR vesicles from the same hearts. This increase in RyR2 activity, however, was not attributable to the PKA-dependent phosphorylation at Ser2809 site. Therefore, the results by MacDonnell et al are in full agreement with our previous findings and confirm in genetically manipulated mice the lack of functionality of the RyR2 Ser 2808/09 site.

The purpose of our . . . [Full Text of this Article]