Frequency-dependent effects of 4-aminopyridine and almokalant on action-potential duration of adult and neonatal rabbit ventricular muscle

The effects of 4-aminopyridine (1 mM) and almokalant (1 mu M) on action-pot ential duration of neonatal and adult rabbit ventricular multicellular prep arations and plateau membrane currents of single ventricular myocytes were studied. In adult ventricular preparations, 4-aminopyridine increased actio n-potential duration in a frequency-dependent manner, with a greater effect at low stimulation frequencies (''reverse" use dependence). In neonatal pr eparations. the increase in action-potential duration by 4-aminopyridine wa s significantly smaller than in adults, and the effect was frequency indepe ndent. Almokalant increased the action-potential duration more in neonatal than in adult myocytes. The effect of almokalant was frequency independent between 0.5 and 2 Hz. The block of transient outward current and delayed re ctifier current in single myocytes was quantitatively similar. We propose t hat differences in the kinetic behavior of the transient outward current be tween adult and neonatal ventricular preparations, slower inactivation, and recovery from inactivation in adults determine differences in the frequenc y-dependent changes induced by 4-aminopyridine and almokalant on action-pot ential duration.