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

American Journal of Physiology - Heart and Circulatory Physiology, ISSN: 0363-6135, Vol: 293, Issue: 4, Page: H2409-17
2007
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Article Description

As a critical step toward understanding the role of abnormal intracellular Ca release via the ryanodine receptor (RyR) 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 RyR hyperphosphorylated at Ser ? 2) Does the spatial distribution of RyR clusters change in failing hearts? Using a newly developed semiquantitative immunohistochemistry method and Western blotting, we measured phosphorylation of RyR at Ser in the spontaneously hypertensive rat (SHR) at four distinct disease stages. A major finding is that hyperphosphorylation of RyR at Ser occurred only at late-stage heart failure in SHR, but not in age-matched controls. Furthermore, the spacing between RyR clusters was shortened in failing hearts, as predicted by quantitative model simulation to increase spontaneous Ca wave generation and arrhythmias. Copyright © 2007 the American Physiological Society.

Bibliographic Details

Ye Chen-Izu; Christopher W. Ward; Wayne Stark Jr.; Tamas Banyasz; Marius P. Sumandea; C. William Balke; Leighton T. Izu; Xander H. T. Wehrens

American Physiological Society

Biochemistry, Genetics and Molecular Biology; Medicine

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