title: Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes.
abstract: Previous studies in adult myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) demonstrated abnormal contractility and intracellular Ca(2+) concentration ([Ca(2+)](i)) homeostasis and decreased sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) expression and activity, but sarcoplasmic reticulum Ca(2+) leak was unchanged. In the present study, we investigated whether SERCA2 overexpression in MI myocytes would restore contraction and [Ca(2+)](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(+)-Ca(2+) exchanger expression but restored the depressed SERCA2 levels toward those measured in sham myocytes. In addition, the reduced sarcoplasmic reticulum Ca(2+) uptake in MI myocytes was improved to normal levels by SERCA2 overexpression. At extracellular Ca(2+) concentration of 5 mM, the subnormal contraction and [Ca(2+)](i) transient amplitudes in MI myocytes (compared with sham myocytes) were restored to normal by SERCA2 overexpression. However, at 0.6 mM extracellular Ca(2+) concentration, the supernormal contraction and [Ca(2+)](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(2+)](i) transient abnormalities in our rat model of ischemic cardiomyopathy. We suggest that other Ca(2+) transport pathways, e.g., Na(+)-Ca(2+) exchanger, may also play an important role in contractile and [Ca(2+)](i) homeostatic abnormalities in MI myocytes.
authors.affiliation: Dept. of Cellular & Molecular Physiology, Milton S. Hershey Medical Center, MC-H166, Hershey, PA 17003, USA.
authors.forename: Belinda A
authors.initials: BA
authors.lastname: Ahlers
authors.forename: Jianliang
authors.initials: J
authors.lastname: Song
authors.forename: JuFang
authors.initials: J
authors.lastname: Wang
authors.forename: Xue-Qian
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Lois L
authors.initials: LL
authors.lastname: Carl
authors.forename: George M
authors.initials: GM
authors.lastname: Tadros
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Rothblum
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Cheung
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D020013:Calcium Signaling; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D020127:Recovery of Function / Q000502:physiology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
chemical_list: C506948:Atp2a2 protein, rat; D011994:Recombinant Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases