Postnatal development has a marked effect on ventricular repolarization in mice

To better understand the mechanisms that underlie cardiac repolarization abnormalities in the immature heart, this study characterized and compared K+ currents in mouse ventricular myocytes from day 1, day 7, day 20, and adult CD1 mice to determine the effects of postnatal development on ventricular repolarization. Current- and patch-clamp techniques were used to examine action potentials and the K+ currents underlying repolarization in isolated myocytes. RT-PCR was used to quantify mRNA expression for the K+ channels of interest. This study found that action potential duration (APD) decreased as age increased, with the shortest APDs observed in adult myocytes. This study also showed that K+ currents and the mRNA relative abundance for the various K+ channels were significantly greater in adult myocytes compared with day 1 myocytes. Examination of the individual components of total K+ current revealed that the inward rectifier K+ current (I-K1) developed by day 7, both the Ca2+-independent transient outward current (I-to) and the steady-state outward K+ current (I-ss) developed by day 20, and the ultrarapid delayed rectifier K+ current (I-Kur) did not fully develop until the mouse reached maturity. Interestingly, the increase in I-Kur was not associated with a decrease in APD. Comparison of atrial and ventricular K+ currents showed that I-to and I-Kur density were significantly greater in day 7, day 20, and adult myocytes compared with age-matched atrial cells. Overall, it appears that, in mouse ventricle, developmental changes in APD are likely attributable to increases in I-to, I-ss, and I-K1, whereas the role of I-Kur during postnatal development appears to be less critical to APD.