Original Article | Published:

Cardiovascular Pharmacology

Cellular mechanisms of reduced sarcoplasmic reticulum Ca2+ content in L-thyroxin-induced rat ventricular hypertrophy

Acta Pharmacologica Sinica volume 29, pages 430436 (2008) | Download Citation

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)

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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Author information

Author notes

    • Lai-jing Song
    •  & Guan-lei Wang

    These authors contributed equally to this work.

Affiliations

  1. Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510089, China

    • Lai-jing Song
    • , Guan-lei Wang
    • , Jie Liu
    • , Qin-ying Qiu
    • , Jing-hua Ou
    •  & Yong-yuan Guan

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Corresponding author

Correspondence to Yong-yuan Guan.

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DOI

https://doi.org/10.1111/j.1745-7254.2008.00763.x

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