Age-related appearance of outward currents may contribute to developmental differences in ventricular repolarization

Abstract

Ventricular repolarization significantly influences contractility, refractoriness, and ion channel state. Factors affecting repolarization will thus affect these secondary phenomena. To understand the influence of age on ventricular repolarization, we studied neonatal, young, and adult dogs using electrocardiogram, action potential, and whole-cell voltage-clamp recordings from single epicardial myocytes. Hearts of neonatal and 57-58-day-old dogs require a significantly longer time for repolarization than those of adult dogs, as determined by analysis of rate-corrected QT and JT (QT minus QRS) intervals. Epicardial action potentials of neonates are significantly longer than those of adults, as determined by measurements of duration at 50% and 90% repolarization. The adult action potential is characterized by a large phase 1 notch that is absent from neonatal recordings. This notch develops between 58 and 64 days of age, and by 64-68 days of age, it is equal to that in adults. In addition, action potentials recorded from adult and young epicardial muscle are more greatly affected by rapid pacing and superfusion of 2 mM 4-aminopyridine than are potentials recorded from neonatal tissue. Whole-cell voltage-clamp recordings reveal a 4-aminopyridine-sensitive transient outward current in adult myocytes that is absent from neonatal myocytes. The correlation between developmental changes in the 4-aminopyridine-sensitive current, the action potential, and the QT interval suggests that the transient outward current may be an important determinant in the relation between age and repolarization.