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Am J Physiol Heart Circ Physiol 279: H1767-H1785, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 4, H1767-H1785, October 2000

Mathematical analysis of canine atrial action potentials: rate, regional factors, and electrical remodeling

Rafael J. Ramirez1,3, Stanley Nattel1,2,4, and Marc Courtemanche1,3,5

1 Research Center, Montreal Heart Institute, Montreal, Quebec H1T 1C8; 2 Department of Pharmacology, McGill University, Montreal, Quebec H3G 1Y6; 3 Institut de Genie Biomedical, 4 Departement de Medecine, and 5 Departement de Physiologie, Universite de Montréal, Montreal, Quebec H3C 3J7, Canada

Dogs have been used extensively to study atrial arrhythmias, but there are no published mathematical models of the canine atrial action potential (AP). To obtain insights into the ionic mechanisms governing canine atrial AP properties, we incorporated formulations of K+, Na+, Ca2+, and Cl- currents, based on measurements in canine atrial myocytes, into a mathematical model of the AP. The rate-dependent behavior of model APs corresponded to experimental measurements and pointed to a central role for L-type Ca2+ current inactivation in rate adaptation. Incorporating previously described regional ionic current variations into the model largely reproduced AP forms characteristic of the corresponding right atrial regions (appendage, pectinate muscle, crista terminalis, and atrioventricular ring). When ionic alterations induced by tachycardia-dependent remodeling were incorporated, the model reproduced qualitatively the AP features constituting the cellular substrate for atrial fibrillation. We conclude that this ionic model of the canine atrial AP agrees well with experimental measurements and gives potential insights into mechanisms underlying functionally important electrophysiological phenomena in canine atrium.

action potential duration; atrial fibrillation; ion channels; rate adaptation; regional heterogeneity; mathematical model


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