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(Circulation Research. 2008;103:e12.)
© 2008 American Heart Association, Inc.

Letters to the Editor

Response to Mattiazzi et al:

Héctor H. Valdivia

Department of Physiology, University of Wisconsin Medical School, Madison, WI

Steven R. Houser

Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pa, E-mail steven.houser@temple.edu

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

Our recent article in Circulation Research¹ has received attention from a number of investigators in the field. Our goal in this research was to explore the hypothesis proposed by Marks and colleagues that PKA-mediated phosphorylation of the ryanodine receptor at Ser2808/09 is a central component of the sympathetic nervous system (SNS) regulation of cardiac contractility.² Our experiments were mainly designed to address this issue. We used a genetically modified mouse in which phosphorylation of Ser2808/09 was eliminated by an alanine substitution (S2809/09A). Our results strongly supported the idea that PKA-mediated phosphorylation of Ser2808/09 has no significant functional role in SNS regulation of cardiac function.

In this issue of Circulation Research, Mattiazzi et al³ have written to the editor regarding our recent report.¹ The purpose of our letter here is to respond to the 3 points made by Mattiazzi et al.³ First, we all agree that there is significant evidence that phosphorylation of Ser2808/09, either by PKA,^2,4 or by CaMKII,^5,6 has little functional significance in the response of the heart to sympathetic stimulation. As we reviewed in our recent report,¹ many laboratories are in agreement on this issue, including Mattiazzi and colleagues,⁶ and this was the major conclusion of our report.

Mattiazzi et al³ point out that there appear to be other PKA phosphorylation sites on RyR2 and that these may have functional significance. Our recent study did not evaluate this possibility; however, Valdivia and colleagues, coauthors in the recent by MacDonnell et al,¹ have been actively involved in this . . . [Full Text of this Article]