© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes
Research Center and Department of Medicine, Montreal Heart Institute, Departments of Medicine and Physiology, University of Montreal, and Department of Pharmacology, McGill University, 5000 Belanger Street East, Montreal, Quebec, Canada H1T 1C8
* Corresponding author. Tel.: +1-514-376-3330; fax: +1-514-376-1355 nattel{at}icm.umontreal.ca
Objectives: Indirect evidence suggests a role for Ca2+-overload in electrical and mechanical alterations caused by atrial tachycardia. The present study assessed the alterations in cellular [Ca2+] and contractile function caused by rapid atrial cellular activation. Methods: Intracellular Ca2+ transients (CaT) and cell shortening (CS) were measured by microfluorometry (Indo-1 AM) and video edge-detection in isolated, field-stimulated canine atrial myocytes (37°C). Results: Abrupt increases in frequency (0.3–3 Hz) caused rapid increases in diastolic [Ca2+]i (DCa) that were maintained during rapid-pacing for up to 50 min. When short-term (3-min) rapid-pacing was imposed, CaT and CS increased initially upon returning to 0.3 Hz, but then declined rapidly to 64±5 and 49±7%, respectively, of pre-tachycardia values, returning to control after 
15 min. Post-tachycardia CaT and CS reductions were prevented by decreasing [Ca2+]o during tachycardia to prevent Ca2+-overload. CS reductions correlated with indices of Ca2+ loading during tachycardia. Restoration of CaT to normal during post-tachycardia contractile dysfunction (by increasing [Ca2+]o) returned CS to normal, indicating that reduced Ca2+ release, not reduced myofilament Ca2+-sensitivity, caused post-tachycardia contractile failure. Estimation of sarcoplasmic-reticulum Ca2+-stores (caffeine-induced Ca2+-release) confirmed tachycardia-induced Ca2+-loading and suggested that reduced Ca2+-stores decreased Ca2+-release post-tachycardia. Conclusions: Atrial tachycardia increases cellular Ca2+-loading, leading to post-tachycardia abnormalities in Ca2+-handling that produce contractile dysfunction. These findings are the first direct evidence for the frequently-postulated role of Ca2+-overload in tachycardia-induced abnormalities of atrial function.
KEYWORDS Arrhythmia (mechanisms); Atrial function; Calcium (cellular); e–c coupling; Remodelling
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