Effects of sarcoplasmic reticulum Ca -ATPase overexpression in postinfarction rat myocytes

Ahlers, Belinda A., Jianliang Song, JuFang Wang, Xue-Qian Zhang, Lois L. Carl, George M. Tadros, Lawrence I. Rothblum, and Joseph Y. Cheung. Effects of sarcoplasmic reticulum Ca -ATPase overexpression in postinfarction rat myocytes. J Appl Physiol 98: 2169–2176, 2005. First published January 27, 2005 ; doi:10.1152/japplphysiol.00013.2005.—Previous studies in adult myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) demonstrated abnormal contractility and intracellular Ca concentration ([Ca ]i) homeostasis and decreased sarcoplasmic reticulum Ca -ATPase (SERCA2) expression and activity, but sarcoplasmic reticulum Ca leak was unchanged. In the present study, we investigated whether SERCA2 overexpression in MI myocytes would restore contraction and [Ca ]i transients to normal. Compared with sham-operated hearts, 3-wk MI hearts exhibited significantly higher left ventricular end-diastolic and endsystolic 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 -Ca exchanger expression but restored the depressed SERCA2 levels toward those measured in sham myocytes. In addition, the reduced sarcoplasmic reticulum Ca uptake in MI myocytes was improved to normal levels by SERCA2 overexpression. At extracellular Ca concentration of 5 mM, the subnormal contraction and [Ca ]i transient amplitudes in MI myocytes (compared with sham myocytes) were restored to normal by SERCA2 overexpression. However, at 0.6 mM extracellular Ca concentration, the supernormal contraction and [Ca ]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 [Ca ]i transient abnormalities in our rat model of ischemic cardiomyopathy. We suggest that other Ca transport pathways, e.g., Na -Ca exchanger, may also play an important role in contractile and [Ca ]i homeostatic abnormalities in MI myocytes.