Rate dependence of action potential duration and refractoriness in canine ventricular endocardium differs from that of epicardium: Role of the transient outward current

AbstractPrevious studies have provided evidence for an important contribution of the transient outward current to the electrical activity of canine ventricular epicardium, but not endocardium. The present study examines the characteristics of action potential duration and refractoriness in these two tissue types. The time and rate dependence of changes in action potential duration and refractoriness observed in epicardium were significantly more accentuated than in endocardium. The restitution of action potential duration in epicardium paralleled the restitution of phase 1 amplitude of the action potential in this tissue. The correlation between phase I amplitude and action potential duration recorded from a large number of epicardial and endocardial preparations was significant under both steady state and restitution conditions. 4-Aminopyridine, a transient outward current blocker, decreased the time dependence of phase I amplitude and concomitantly decreased the time dependence of action potential duration in epicardium. 4-Aminopyridine abbreviated the action potential duration of epicardium at slow stimulation rates but had little effect or prolonged it at fast rates or after premature stimulation. (The availability of a transient outward current is relatively small after premature stimulation.)The data support the hypothesis that the prominent presence of a transient outward current in epicardium, but not endocardium, contributes to the differences in the time and rate dependence of action potential duration and refractoriness in the two tissue types. The results also demonstrate the effect of an outward current to prolongthe action potential and the effect of an outward current blocker to abbreviatethe action potential. These observations may also aid in our understanding of the basis for rate-dependent changes in the T wave and 1 wave of the electrocardiogram, the rate dependence of cardiac arrhythmias, the greater sensitivity of epicardium to ischemia and the differential effects of drugs on muscle tissues spanning the ventricular wall