{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T15:44:47Z","timestamp":1771515887847,"version":"3.50.1"},"reference-count":49,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:p>As a critical step toward understanding the role of abnormal intracellular Ca<jats:sup>2+<\/jats:sup>release via the ryanodine receptor (RyR<jats:sub>2<\/jats:sub>) 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<jats:sub>2<\/jats:sub>hyperphosphorylated at Ser<jats:sup>2808<\/jats:sup>? 2) Does the spatial distribution of RyR<jats:sub>2<\/jats:sub>clusters change in failing hearts? Using a newly developed semiquantitative immunohistochemistry method and Western blotting, we measured phosphorylation of RyR<jats:sub>2<\/jats:sub>at Ser<jats:sup>2808<\/jats:sup>in the spontaneously hypertensive rat (SHR) at four distinct disease stages. A major finding is that hyperphosphorylation of RyR<jats:sub>2<\/jats:sub>at Ser<jats:sup>2808<\/jats:sup>occurred only at late-stage heart failure in SHR, but not in age-matched controls. Furthermore, the spacing between RyR<jats:sub>2<\/jats:sub>clusters was shortened in failing hearts, as predicted by quantitative model simulation to increase spontaneous Ca<jats:sup>2+<\/jats:sup>wave generation and arrhythmias.<\/jats:p>","DOI":"10.1152\/ajpheart.00562.2007","type":"journal-article","created":{"date-parts":[[2007,7,14]],"date-time":"2007-07-14T01:14:54Z","timestamp":1184375694000},"page":"H2409-H2417","source":"Crossref","is-referenced-by-count":47,"title":["Phosphorylation of RyR<sub>2<\/sub>and shortening of RyR<sub>2<\/sub>cluster spacing in spontaneously hypertensive rat with heart failure"],"prefix":"10.1152","volume":"293","author":[{"given":"Ye","family":"Chen-Izu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher W.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Wayne","family":"Stark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamas","family":"Banyasz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius P.","family":"Sumandea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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