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This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 98/6/2169    most recent 00013.2005v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Ahlers, B. A. Articles by Cheung, J. Y. Search for Related Content PubMed PubMed Citation Articles by Ahlers, B. A. Articles by Cheung, J. Y.

Effects of sarcoplasmic reticulum Ca²⁺-ATPase overexpression in postinfarction rat myocytes

¹Departments of Cellular and Molecular Physiology and ²Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey; and ³Weis Center for Research, Geisinger Medical Center, Danville, Pennsylvania

Submitted 4 January 2005 ; accepted in final form 24 January 2005

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.

primary cardiac myocyte culture; fura 2; excitation-contraction coupling; gene transfer