Developmental Changes in Transient Outward Current in Mouse Ventricle

Abstract

Abstract 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±4 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.