Ionic Mechanisms of Regional Action Potential Heterogeneity in the Canine Right Atrium

From the Department of Medicine (Z.W., S.N.) and Research Center (J.F., L.Y., Z.W., S.N.), Montreal Heart Institute; the Department of Medicine (Z.W., S.N.), University of Montreal; and the Department of Pharmacology and Therapeutics (L.Y., S.N.), McGill University, Montreal, Quebec, Canada.

Correspondence to Dr Stanley Nattel, MD, Research Center, Montreal Heart Institute, 5000 Belanger St East, Montreal, Quebec H1T 1C8 Canada. E-mail nattel{at}icm.umontreal.ca

Abstract—Atrial action potential heterogeneity is a major determinant of atrial reentrant arrhythmias, but the underlying ionic mechanisms are poorly understood. To evaluate the basis of spatial heterogeneity in canine right atrial repolarization, we isolated cells from 4 regions: the crista terminalis (CT), appendage (APG), atrioventricular ring (AVR) area, and pectinate muscles. Systematic action potential (AP) differences were noted: CT cells had a "spike-and-dome" morphology and the longest AP duration (APD; value to 95% repolarization at 1 Hz, 270±10 ms [mean±SEM]); APG and pectinate muscle cells had intermediate APDs (180±3 and 190±3 ms, respectively; P<0.001 versus CT for each), with APG cells having a small phase 1; and AVR cells had the shortest APD (160±4 ms, P<0.001 versus other regions). The inward rectifier and the slow and ultrarapid delayed rectifier currents were similar in all regions. The transient outward K⁺ current was significantly smaller in APG cells, explaining their small phase 1 and high plateau. L-type Ca²⁺ current was greatest in CT cells and least in AVR cells, contributing to their longer and shorter APD, respectively. The E-4031–sensitive rapid delayed rectifier K⁺ current was larger in AVR cells compared with other regions. Voltage- and time-dependent current properties were constant across regions. We conclude that myocytes from different right atrial regions of the dog show systematic variations in AP properties and ionic currents and that the spatial variation in ionic current density may explain AP differences. Regional variation in atrial ionic currents may play an important role in atrial arrhythmia generation and may present opportunities for improving antiarrhythmic drug therapy.

Key Words: ion channel • cardiac arrhythmia • atrial fibrillation • action potential duration • regional heterogeneity

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