Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes.
OBJECTIVE
Indirect evidence suggests a role for Ca(2+)-overload in electrical and mechanical alterations caused by atrial tachycardia. The present study assessed the alterations in cellular [Ca(2+)] and contractile function caused by rapid atrial cellular activation.


METHODS
Intracellular Ca(2+) 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 degrees C).


RESULTS
Abrupt increases in frequency (0.3-3 Hz) caused rapid increases in diastolic [Ca(2+)]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 approximately 15 min. Post-tachycardia CaT and CS reductions were prevented by decreasing [Ca(2+)]o during tachycardia to prevent Ca(2+)-overload. CS reductions correlated with indices of Ca(2+) loading during tachycardia. Restoration of CaT to normal during post-tachycardia contractile dysfunction (by increasing [Ca(2+)]o) returned CS to normal, indicating that reduced Ca(2+) release, not reduced myofilament Ca(2+)-sensitivity, caused post-tachycardia contractile failure. Estimation of sarcoplasmic-reticulum Ca(2+)-stores (caffeine-induced Ca(2+)-release) confirmed tachycardia-induced Ca(2+)-loading and suggested that reduced Ca(2+)-stores decreased Ca(2+)-release post-tachycardia.


CONCLUSIONS
Atrial tachycardia increases cellular Ca(2+)-loading, leading to post-tachycardia abnormalities in Ca(2+)-handling that produce contractile dysfunction. These findings are the first direct evidence for the frequently-postulated role of Ca(2+)-overload in tachycardia-induced abnormalities of atrial function.
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, H1T 1C8, Canada.
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D003592:Cytophotometry; D004285:Dogs; D004558:Electric Stimulation; D006325:Heart Atria; D007424:Intracellular Fluid / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013610:Tachycardia / Q000378:metabolism*
D002118:Calcium