Developmental changes in transient outward current in mouse ventricle.

Developmental changes in the transient outward K+ current (Ito) in mouse ventricular myocytes were assessed by the whole-cell patch-clamp technique. The density of Ito in mouse ventricular myocytes was significantly increased from the day-1 neonate to the adult. At +50 mV, the density of Ito was 3 +/- 1 pA/pF in the day-1 neonate, 15 +/- 3 pA/pF in the day-14 neonate, and 19 +/- 4 pA/pF in the adult (P < .01). Unlike other species, the rate of Ito inactivation significantly slowed in mouse ventricular cells during development. Moreover, the time courses of inactivation and recovery from inactivation of Ito were well described by a monoexponential function in day-1 neonatal cells, whereas they were best fitted by a biexponential function in day-14 neonatal and adult cells. The characteristics of steady state inactivation were also significantly different in day-1 neonatal cells (half-inactivation potential [Vh] = -66 +/- 4 mV, slope factor [k] = 12 +/- 2 mV), in day-14 neonatal cells (Vh = -40 +/- 3 mV, k = 13 +/- 1 mV), and in adult cells (Vh = -34 +/- 4 mV, k = 6 +/- 1 mV). Microelectrode studies revealed that action potential duration progressively decreased in mouse ventricles during normal postnatal development. In addition, 4-aminopyridine (1 mmol/L) prolonged action potential duration more in adult than in neonatal mouse ventricles, suggesting that the developmental increase in the density of Ito contributes to the age-related shortening of action potential duration in mouse ventricles. In conclusion, Ito in adult mouse ventricular myocytes exhibits a higher density, slower inactivation kinetics, and a relatively more positive half-inactivation potential. All these characteristics result in Ito being a physiologically more important repolarizing K+ current in adult than in neonatal mouse hearts.