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

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Abstract
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.