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.

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