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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/H2409    most recent 00562.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Chen-Izu, Y. Articles by Wehrens, X. H. T. Search for Related Content PubMed PubMed Citation Articles by Chen-Izu, Y. Articles by Wehrens, X. H. T.

Phosphorylation of RyR₂ and shortening of RyR₂ cluster spacing in spontaneously hypertensive rat with heart failure

¹Departments of Internal Medicine and Physiology, University of Kentucky College of Medicine, Lexington, Kentucky; ²School of Nursing and ³School of Medicine, University of Maryland, Baltimore, Maryland; ⁴Department of Physiology, University Medical School of Debrecen, Debrecen, Hungary; and ⁵Departments of Molecular Physiology and Biophysics, and Medicine (Cardiology), Baylor College of Medicine, Houston, Texas

Submitted 14 May 2007 ; accepted in final form 11 July 2007

As a critical step toward understanding the role of abnormal intracellular Ca²⁺ release via the ryanodine receptor (RyR₂) during the development of hypertension-induced cardiac hypertrophy and heart failure, this study examines two questions: 1) At what stage, if ever, in the development of hypertrophy and heart failure is RyR₂ hyperphosphorylated at Ser²⁸⁰⁸? 2) Does the spatial distribution of RyR₂ clusters change in failing hearts? Using a newly developed semiquantitative immunohistochemistry method and Western blotting, we measured phosphorylation of RyR₂ at Ser²⁸⁰⁸ in the spontaneously hypertensive rat (SHR) at four distinct disease stages. A major finding is that hyperphosphorylation of RyR₂ at Ser²⁸⁰⁸ occurred only at late-stage heart failure in SHR, but not in age-matched controls. Furthermore, the spacing between RyR₂ clusters was shortened in failing hearts, as predicted by quantitative model simulation to increase spontaneous Ca²⁺ wave generation and arrhythmias.

ryanodine receptor; hypertension; cardiac hypertrophy; protein kinase A; spontaneously hypertensive rat

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