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

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

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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 Ser 2808? 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 Ca 2+ wave generation and arrhythmias.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number4
DOIs
StatePublished - Oct 2007
Externally publishedYes

Keywords

  • Cardiac hypertrophy
  • Hypertension
  • Protein kinase A
  • Ryanodine receptor
  • Spontaneously hypertensive rat

ASJC Scopus subject areas

  • Physiology

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