Cellular mechanisms of reduced sarcoplasmic reticulum Ca^2＋ content in L-thyroxin-induced rat ventricular hypertrophy  

作　　者：Lai-jing SONG Guan-lei WANG Jie LIU Qin-ying QIU Jing-hua OU Yong-yuan GUAN 

机构地区：[1]Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510089, China

出　　处：《Acta Pharmacologica Sinica》2008年第4期430-436,共7页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China （№ 30271503 and No 30730105） and by Science Foundation of Ministry of Education in China （№ 20050558072）Acknowledgments We thank Prof Jian-xin SHEN （Department of Physiology, University of Shan Tou） and Yan-qiu FENG （Department of Biomedical Engineering, The Southern Medical University） for their help with the Ca^2＋ spark recording.

摘　　要：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 Ca2~ 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.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 Ca2~ 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.

关 键 词：left ventricular hypertrophy sarcoplasmic reticulum Ca^2＋ release Ca2＋-ATPase 

分 类 号：R541[医药卫生—心血管疾病]