Exercise training corrects control of spontaneous calcium waves in hearts from myocardial infarction heart failure rats

Ole J. Kemi*, Niall MacQuaide, Morten A. Hoydal, Oyvind Ellingsen, Godfrey L Smith, Ulrik Wisloff

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Impaired cardiac control of intracellular diastolic Ca(2+) gives rise to arrhythmias. Whereas exercise training corrects abnormal cyclic Ca(2+) handling in heart failure, the effect on diastolic Ca(2+) remains unstudied. Here, we studied the effect of exercise training on the generation and propagation of spontaneous diastolic Ca(2+) waves in failing cardiomyocytes. Post-myocardial infarction heart failure was induced in Sprague-Dawley rats by coronary artery ligation. Echocardiography confirmed left ventricular infarctions of 40 ± 5%, whereas heart failure was indicated by increased left ventricular end-diastolic pressures, decreased contraction-relaxation rates, and pathological hypertrophy. Spontaneous Ca(2+) waves were imaged by laser linescanning confocal microscopy (488 nm excitation/505-530 nm emission) in 2 µM Fluo-3-loaded cardiomyocytes at 37°C and extracellular Ca(2+) of 1.2 and 5.0 mM. These studies showed that spontaneous Ca(2+) wave frequency was higher at 5.0 mM than 1.2 mM extracellular Ca(2+) in all rats, but failing cardiomyocytes generated 50% (P < 0.01) more waves compared to sham-operated controls at Ca(2+) 1.2 and 5.0 mM. Exercise training reduced the frequency of spontaneous waves at both 1.2 and 5.0 mM Ca(2+) (P < 0.05), although complete normalization was not achieved. Exercise training also increased the aborted/completed ratio of waves at 1.2 mM Ca(2+) (P < 0.01), but not 5.0 mM. Finally, we repeated these studies after inhibiting the nitric oxide synthase with L-NAME. No differential effects were found; thus, mediation did not involve the nitric oxide synthase. In conclusion, exercise training improved the cardiomyocyte control of diastolic Ca(2+) by reducing the Ca(2+) wave frequency and by improving the ability to abort spontaneous Ca(2+) waves after their generation, but before cell-wide propagation.

Original languageEnglish
Pages (from-to)20-26
Number of pages7
JournalJournal of Cellular Physiology
Volume227
Issue number1
Early online date24 Oct 2011
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Animals
  • Calcium/metabolism
  • Female
  • Heart/physiopathology
  • Heart Failure/metabolism
  • Microscopy, Confocal
  • Myocardial Infarction/metabolism
  • Myocytes, Cardiac/metabolism
  • Physical Conditioning, Animal/physiology
  • Rats
  • Rats, Sprague-Dawley

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