Cellular mechanisms of reduced sarcoplasmic reticulum Ca2+ content in L-thyroxin induced rat ventricular hypertrophy.
OBJECTIVE
To examine how the sarcoplasmic reticulum (SR) Ca2+ 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 Ca2+ concentration ([Ca2+]i), the Ca2+ sparks, and the caffeine-induced Ca2+ transient in freshly isolated cardiac ventricular myocytes. The activity of sarcolemmal and SR Ca2+-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 Ca2+ transient in the Ca2+-free solution was detected. The spontaneous Ca2+ sparks in hypertrophied myocytes occurred more frequently than in normal cells, with similar duration and spatial spread, but smaller amplitude. Then the basal [Ca2+]i increase was observed in quiescent left ventricular myocytes from hyperthyroidism rats. The activity of sarcolemmal and SR Ca2+-ATPase was decreased in the hypertrophied ventricle tissue.


CONCLUSIONS
The results suggested that the reduced SR Ca2+ content may be associated with an increased Ca2+ leak and reduced SERCA2a activity, contributing to abnormal intracellular Ca2+ handling during hypertrophy in hyperthyroidism rats.
Song
Lai-jing
LJ
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510089, China.
Wang
Guan-lei
GL
Liu
Jie
J
Qiu
Qin-ying
QY
Ou
Jing-hua
JH
Guan
Yong-yuan
YY
D000818:Animals; D002110:Caffeine / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology; D004562:Electrocardiography; D006352:Heart Ventricles / Q000166:cytology; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000032:analysis / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism / Q000494:pharmacology*
D002110:Caffeine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013974:Thyroxine; D002118:Calcium