Developmental changes in transient outward current in mouse ventricle

Developmental changes in the transient outward K+ current (I-to) in mouse ventricular myocytes were assessed by the whole-cell patch-clamp technique. The density of I-to in mouse ventricular myocytes was significantly increased from the day-1 neonate to the adult. At +50 mV, the density of I-to 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 I-to inactivation significantly slowed in mouse ventricular cells during development. Moreover, the time courses of inactivation and recovery from inactivation of I-to, 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 [V-h]=-66+/-3 mV, slope factor [k]=12+/-2 mV), in day-14 neonatal cells (V-h=-40+/-3 mV, k=13+/-1 mV), and in adult cells (V-h=-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 I-to contributes to the age-related shortening of action potential duration in mouse ventricles. In conclusion, I-to 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 I-to being a physiologically more important repolarizing K+ current in adult than in neonatal mouse hearts.