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

Kemi, O. J. , MacQuaide, N. , Hoydal, M. A., Ellingsen, O., Smith, G. L. and Wisloff, U. (2012) Exercise training corrects control of spontaneous calcium waves in hearts from myocardial infarction heart failure rats. Journal of Cellular Physiology, 227(1), pp. 20-26. (doi: 10.1002/jcp.22771)

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Abstract

Impaired cardiac control of intracellular diastolic Ca<sup>2+</sup> gives rise to arrhythmias. Whereas exercise training corrects abnormal cyclic Ca<sup>2+</sup> handling in heart failure, the effect on diastolic Ca<sup>2+</sup> remains unstudied. Here, we studied the effect of exercise training on the generation and propagation of spontaneous diastolic Ca<sup>2+</sup> 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<sup>2+</sup> 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<sup>2+</sup> of 1.2 and 5.0 mM. These studies showed that spontaneous Ca<sup>2+</sup> wave frequency was higher at 5.0 mM than 1.2 mM extracellular Ca<sup>2+</sup> in all rats, but failing cardiomyocytes generated 50% (P < 0.01) more waves compared to sham-operated controls at Ca<sup>2+</sup> 1.2 and 5.0 mM. Exercise training reduced the frequency of spontaneous waves at both 1.2 and 5.0 mM Ca2+ (P< 0.05), although complete normalization was not achieved. Exercise training also increased the aborted/completed ratio of waves at 1.2 mM Ca<sup>2+</sup> (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<sup>2+</sup> by reducing the Ca<sup>2+</sup> wave frequency and by improving the ability to abort spontaneous Ca<sup>2+</sup> waves after their generation, but before cell-wide propagation.

Item Type:Articles
Additional Information:The definitive version is available at www3.interscience.wiley.com
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and MacQuaide, Dr Niall and Kemi, Dr Ole
Authors: Kemi, O. J., MacQuaide, N., Hoydal, M. A., Ellingsen, O., Smith, G. L., and Wisloff, U.
Subjects:Q Science > QP Physiology
R Medicine > RC Internal medicine > RC1200 Sports Medicine
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Cellular Physiology
Journal Abbr.:J. Cell Physiol.
Publisher:Wiley
ISSN:0021-9541
ISSN (Online):1097-4652
Published Online:24 October 2011
Copyright Holders:Copyright © 2011 Wiley-Liss, Inc.
First Published:First published in Journal of Cellular Physiology 227(1):20-26
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher
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