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Transmembrane action potential heterogeneity in the canine isolated arterially perfused right atrium: effect of I_Kr and I_Kur/I_to block

Masonic Medical Research Laboratory, Utica, New York 13501

Submitted 30 December 2003 ; accepted in final form 4 February 2004

The role of electrical heterogeneity in development of cardiac arrhythmias is well recognized. The extent to which transmembrane action potential (TAP) heterogeneity contributes to the normal electrophysiology of well-oxygenated atria is not well defined. The principal objective of the present study was to define regional and transmural differences in characteristics of the TAP in isolated superfused and arterially perfused canine right atrial (RA) preparations under baseline, rapidly activating delayed rectifier K⁺ current (I_Kr) block, and combined block of ultrarapid delayed rectifier and transient outward K⁺ current (I_Kur/I_to block). Superfused preparations that survived generally displayed a triangle-shaped TAP. Exceptions included cells from the crista terminalis, where TAPs with a normal plateau could be recorded. In contrast, most TAPs recorded from throughout the perfused RA displayed a spike-and-dome and/or plateau morphology. The perfused RA displayed a heterogeneous distribution of repolarization, V_max, and spike-and-dome morphology along the epicardial and endocardial surfaces as well as transmurally, in the region of the upper crista terminalis. I_Kr block with E-4031 prolonged repolarization homogeneously in the perfused RA, whereas I_Kur/I_to block using low concentrations of 4-aminopyridine abbreviated action potential duration at 90% repolarization heterogeneously, leading to a reduction in dispersion of repolarization. Our data indicate that the electrical heterogeneities, previously described for the canine ventricle, also exist within the atria and that I_Kr block does not accentuate and I_Kur/I_to block reduces RA dispersion of repolarization. Our study also points to major differences in the transmembrane activity recorded using superfused vs. arterially perfused atrial preparations.

atrial electrophysiology; atrial pharmacology; arrhythmias

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