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In situ SR function in postinfarction myocytes.

X Q Zhang1, Y C Ng, R L Moore

  • 1Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033, USA.

Journal of Applied Physiology (Bethesda, Md. : 1985)
|December 22, 1999
PubMed
Summary
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Myocardial infarction (MI) in rats reduces sarcoplasmic reticulum (SR) Ca(2+) content due to decreased SR Ca(2+)-ATPase activity, not increased SR Ca(2+) leak. This impacts cardiac myocyte function after heart attack.

Area of Science:

  • Cardiovascular Physiology
  • Cardiac Excitation-Contraction Coupling
  • Molecular Cardiology

Background:

  • Myocardial infarction (MI) leads to reduced intracellular Ca(2+) ([Ca(2+)](i)) and sarcoplasmic reticulum (SR) Ca(2+) content in cardiac myocytes.
  • Previous studies indicate normal L-type Ca(2+) channel activity but depressed reverse Na(+)/Ca(2+) exchange in MI myocytes.

Purpose of the Study:

  • To investigate the mechanisms responsible for reduced SR Ca(2+) content in cardiac myocytes following myocardial infarction.
  • To differentiate between impaired SR Ca(2+) uptake and enhanced SR Ca(2+) leak as causes of diminished SR Ca(2+) stores.

Main Methods:

  • Intact cardiac myocytes from sham and MI rats were used to measure SR Ca(2+) uptake and leak in situ.
  • SR Ca(2+) uptake was assessed by measuring the half-time (t(1/2)) of intracellular Ca(2+) transient decline after caffeine application.

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  • SR Ca(2+) leak was quantified using a novel electrophysiological technique.
  • Main Results:

    • MI myocytes exhibited significantly lower systolic [Ca(2+)](i) and a prolonged t(1/2) of [Ca(2+)](i) decline, indicating reduced SR Ca(2+) uptake.
    • A 19% prolongation in t(1/2) correlated with a 23% decrease in SR Ca(2+)-ATPase expression in MI myocytes.
    • No significant difference in SR Ca(2+) leak rate was observed between sham and MI myocytes.

    Conclusions:

    • Reduced SR Ca(2+) content in MI myocytes is primarily caused by impaired SR Ca(2+) uptake, specifically due to decreased SR Ca(2+)-ATPase expression.
    • Enhanced SR Ca(2+) leak does not contribute to the diminished SR Ca(2+) stores after myocardial infarction.