Exercise training corrects control of spontaneous calcium waves in hearts from myocardial infarction heart failure rats
✍ Scribed by Ole J. Kemi; Niall MacQuaide; Morten A. Hoydal; Oyvind Ellingsen; Godfrey L. Smith; Ulrik Wisloff
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 447 KB
- Volume
- 227
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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. J. Cell. Physiol. 227: 20–26, 2012. © 2011 Wiley Periodicals, Inc.