Cellular mechanisms of reduced sarcoplasmic reticulum Ca2+ content in L-thyroxin-induced rat ventricular hypertrophy
Authors: SONG, Lai-jing; WANG, Guan-lei; LIU, Jie; QIU, Qin-ying; OU, Jing-hua; GUAN, Yong-yuan
Source: Acta Pharmacologica Sinica, Volume 29, Number 4, April 2008 , pp. 430-436(7)
Aim: 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. Conclusion: 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.
Document Type: Research Article
Affiliations: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510089, China
Publication date: April 1, 2008