title: Exercise training corrects control of spontaneous calcium waves in hearts from myocardial infarction heart failure rats.
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.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UK. Ole.Kemi@glasgow.ac.uk
authors.forename: Ole J
authors.initials: OJ
authors.lastname: Kemi
authors.forename: Niall
authors.initials: N
authors.lastname: MacQuaide
authors.forename: Morten A
authors.initials: MA
authors.lastname: Hoydal
authors.forename: Oyvind
authors.initials: O
authors.lastname: Ellingsen
authors.forename: Godfrey L
authors.initials: GL
authors.lastname: Smith
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wisloff
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology / Q000534:rehabilitation; D018613:Microscopy, Confocal; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000534:rehabilitation*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002118:Calcium