Key result
SERCA2 overexpression in post-MI rat myocytes restored contraction at 5 mM extracellular Ca2+ but exacerbated abnormalities at 0.6 mM, showing only partial effectiveness.
Why the study?
Does SERCA2 overexpression restore contraction and [Ca2+]i transients to normal in postinfarction rat myocytes?
Does SERCA2 overexpression restore contraction and [Ca2+]i transients to normal in postinfarction rat myocytes?
SERCA2 overexpression is only partially effective in ameliorating contraction and Ca2+ transient abnormalities in a rat model of ischemic cardiomyopathy, suggesting other pathways like the Na+-Ca2+ exchanger play important roles.
Only partial effectiveness of SERCA2 overexpression in post-MI rat myocytes; leaves open roles for Na+-Ca2+ exchanger and other pathways in ischemic cardiomyopathy.
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.
No takes yet. Share an insight, caveat, or question.
Ahlers et al. (2005) studied Myocardial infarction. SERCA2 overexpression vs. Sham myocytes was evaluated on Contraction and [Ca(2+)](i) transients. SERCA2 overexpression in post-MI rat myocytes restored contraction at 5 mM extracellular Ca2+ but exacerbated abnormalities at 0.6 mM, showing only partial effectiveness.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: