In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 293, No. 4 ( 2007-10), p. H2409-H2417
Abstract:
As a critical step toward understanding the role of abnormal intracellular Ca 2+ release via the ryanodine receptor (RyR 2 ) 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 2 hyperphosphorylated at Ser 2808 ? 2) Does the spatial distribution of RyR 2 clusters change in failing hearts? Using a newly developed semiquantitative immunohistochemistry method and Western blotting, we measured phosphorylation of RyR 2 at Ser 2808 in the spontaneously hypertensive rat (SHR) at four distinct disease stages. A major finding is that hyperphosphorylation of RyR 2 at Ser 2808 occurred only at late-stage heart failure in SHR, but not in age-matched controls. Furthermore, the spacing between RyR 2 clusters was shortened in failing hearts, as predicted by quantitative model simulation to increase spontaneous Ca 2+ wave generation and arrhythmias.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00562.2007
Language:
English
Publisher:
American Physiological Society
Publication Date:
2007
detail.hit.zdb_id:
1477308-9
SSG:
12