Open AccessCellular mechanisms of reduced sarcoplasmic reticulum Ca 2+ content in L ‐thyroxin‐induced rat ventricular hypertrophy 1
Author(s) -
SONG Laijing,
WANG Guanlei,
LIU Jie,
QIU Qinying,
OU Jinghua,
GUAN Yongyuan
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00763.x
Subject(s) - endoplasmic reticulum , muscle hypertrophy , medicine , cardiac hypertrophy , endocrinology , chemistry , biology , biochemistry
Abstract Aim: To examine how the sarcoplasmic reticulum (SR) Ca 2+ content changes and the underlying mechanism in L ‐thyroxin‐induced cardiac hypertrophy. Methods: Echocardiography was used to confirm the establishment of the cardiac hypertrophy model. The confocal microscopy and fluorescent indicator Fluo‐3 was applied to examine the intracellular Ca 2+ concentration ([Ca 2+ ] i ), the Ca 2+ sparks, and the caffeine‐induced Ca 2+ transient in freshly isolated cardiac ventricular myocytes. The activity of sarcolemmal and SR Ca 2+ ‐ATPase 2a (SERCA2a) in the ventricular tissue was also measured, respectively. Results: L ‐thyroxin (1 mg/kg injection for 10 d) induces left ventricular cardiac hypertrophy with normal myocardial function. The decreased caffeine‐induced Ca 2+ transient in the Ca 2+ ‐free solution was detected. The spontaneous Ca 2+ sparks in hypertrophied myocytes occurred more frequently than in normal cells, with similar duration and spatial spread, but smaller amplitude. Then the basal [Ca 2+ ] i increase was observed in quiescent left ventricular myocytes from hyperthyroidism rats. The activity of sarcolemmal and SR Ca 2+ ‐ATPase was decreased in the hypertrophied ventricle tissue. Conclusion: The results suggested that the reduced SR Ca 2+ content may be associated with an increased Ca 2+ leak and reduced SERCA2a activity, contributing to abnormal intracellular Ca 2+ handling during hypertrophy in hyperthyroidism rats.