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 Ca(2+)-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.
Research Center, Montreal Heart Institute, and Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
Scott A
SA
Grandy
Véronique
V
Trépanier-Boulay
Céline
C
Fiset
D000200:Action Potentials; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006325:Heart Atria / Q000378:metabolism; D006329:Heart Conduction System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D007700:Kinetics; D051605:Kv Channel-Interacting Proteins / Q000378:metabolism; D051666:Kv1.5 Potassium Channel / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012107:Research Design; D051669:Shab Potassium Channels / Q000378:metabolism; D051672:Shal Potassium Channels / Q000378:metabolism; D013045:Species Specificity
C496991:Kcnb1 protein, rat; C489461:Kir2.1 channel; D051605:Kv Channel-Interacting Proteins; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D051672:Shal Potassium Channels; D011188:Potassium