Submitted on January 4, 2005
Accepted on January 24, 2005
Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes
Belinda A. Ahlers1, Jianliang Song1, JuFang Wang1, Xue-Qian Zhang1, Lois L. Carl1, George M. Tadros2, Lawrence I. Rothblum2, and Joseph Y. Cheung3*
1 Department of Cellular and Molecular Physiology, Pennsylvania State University, Hershey, PA, USA; Weis Center for Research, Geisinger Medical Center, Danville, PA, USA
2 Weis Center for Research, Geisinger Medical Center, Danville, PA, USA
3 Department of Cellular and Molecular Physiology, Pennsylvania State University, Hershey, PA, USA; Department of Medicine, Pennsylvania State University, Hershey, PA, USA; Weis Center for Research, Geisinger Medical Center, Danville, PA, USA
* To whom correspondence should be addressed. E-mail: jyc1{at}psu.edu.
Previous studies in adult myocytes isolated from rat hearts 3 weeks after myocardial infarction (MI) demonstrated abnormal contractility and intracellular Ca2+ concentration ([Ca2+]i) homeostasis, decreased sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2) expression and activity, but SR 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 to sham-operated hearts, 3 week
MI hearts exhibited significantly higher left ventricular (LV) end-diastolic and endsystolic volumes, but lower fractional shortening and ejection fraction as measured by Mmode echocardiography. Seventy-two hours after adenovirus-mediated gene transfer, SERCA2 overexpression in 3 week MI myocytes did not affect Na+/Ca2+ exchanger expression, but restored the depressed SERCA2 levels towards those measured in sham myocytes. In addition, the reduced SR Ca2+ uptake in MI myocytes was improved to normal levels by SERCA2 overexpression. At extracellular Ca2+ concentration ([Ca2+]o) 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 0.6mM [Ca2+]o, 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.
