Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes
| Autor: | Joseph Y. Cheung, George M. Tadros, Jianliang Song, Lawrence I. Rothblum, Belinda A. Ahlers, Lois L. Carl, Xue-Qian Zhang, JuFang Wang |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Contraction (grammar) Fura-2 Physiology Myocardial Infarction chemistry.chemical_element Calcium-Transporting ATPases Biology Calcium Gene Expression Regulation Enzymologic Sarcoplasmic Reticulum Calcium-Transporting ATPases Rats Sprague-Dawley Contractility chemistry.chemical_compound Physiology (medical) Internal medicine medicine Animals Myocyte Myocytes Cardiac Calcium Signaling Cells Cultured Calcium signaling Endoplasmic reticulum Recovery of Function Adaptation Physiological Myocardial Contraction Recombinant Proteins Rats Endocrinology chemistry Homeostasis |
| Zdroj: | Journal of Applied Physiology. 98:2169-2176 |
| ISSN: | 1522-1601 8750-7587 |
| DOI: | 10.1152/japplphysiol.00013.2005 |
| Popis: | Previous studies in adult myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) demonstrated abnormal contractility and intracellular Ca2+ concentration ([Ca2+]i) homeostasis and decreased sarcoplasmic reticulum Ca2+-ATPase (SERCA2) expression and activity, but sarcoplasmic reticulum Ca2+ leak was unchanged. In the present study, we investigated whether SERCA2 overexpression in MI myocytes would restore contraction and [Ca2+]i transients to normal. Compared with sham-operated hearts, 3-wk MI hearts exhibited significantly higher left ventricular end-diastolic and end-systolic volumes but lower fractional shortening and ejection fraction, as measured by M-mode echocardiography. Seventy-two hours after adenovirus-mediated gene transfer, SERCA2 overexpression in 3-wk MI myocytes did not affect Na+-Ca2+ exchanger expression but restored the depressed SERCA2 levels toward those measured in sham myocytes. In addition, the reduced sarcoplasmic reticulum Ca2+ uptake in MI myocytes was improved to normal levels by SERCA2 overexpression. At extracellular Ca2+ concentration of 5 mM, the subnormal contraction and [Ca2+]i transient amplitudes in MI myocytes (compared with sham myocytes) were restored to normal by SERCA2 overexpression. However, at 0.6 mM extracellular Ca2+ concentration, the supernormal contraction and [Ca2+]i transient amplitudes in MI myocytes (compared with sham myocytes) were exacerbated by SERCA2 overexpression. We conclude that SERCA2 overexpression was only partially effective in ameliorating contraction and [Ca2+]i transient abnormalities in our rat model of ischemic cardiomyopathy. We suggest that other Ca2+ transport pathways, e.g., Na+-Ca2+ exchanger, may also play an important role in contractile and [Ca2+]i homeostatic abnormalities in MI myocytes. |
| Databáze: | OpenAIRE |
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