Abstract
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.
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Project supported by the National Natural Science Foundation of China (No 30271503 and No 30730105) and by Science Foundation of Ministry of Education in China (No 20050558072)
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Song, Lj., Wang, Gl., Liu, J. et al. Cellular mechanisms of reduced sarcoplasmic reticulum Ca2+ content in L-thyroxin-induced rat ventricular hypertrophy. Acta Pharmacol Sin 29, 430–436 (2008). https://doi.org/10.1111/j.1745-7254.2008.00763.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00763.x