Postnatal development of atrial repolarization in the mouse.
OBJECTIVE
This study examines postnatal development of action potential duration (APD) and voltage-dependent K(+) currents in mouse atrial myocytes and compares the expression levels of corresponding K(+) channels between adult and neonatal mouse atrial tissues. APD and K(+) currents were compared between atrial myocytes isolated from postnatal Day-1, Day-7, Day-20, and adult mice.


RESULTS
All K(+) currents examined underwent significant up-regulation during postnatal life in mouse atrium, resulting in a dramatic shortening of the APD. The ultrarapid delayed rectifier (I(Kur)) was absent in the developing mouse heart and only contributed to repolarization in the adult mouse atrium, whereas the density of the other K(+) currents increased earlier during the developmental period. Indeed, the major changes in the expression of the inward rectifier current (I(K1)) occurred within the first week of life, the density of the Ca(2+)-independent transient outward K(+) current (I(to)) gradually increased while the development of the steady-state outward K(+) current (I(ss)) was completed within the first 3 weeks of life. Results of RNase protection assay and Western blot analysis confirmed that the postnatal development of the mouse atrial K(+) currents correlates with an increase in expression levels of underlying K(+) channel isoforms.


CONCLUSIONS
These findings indicate that in mouse atrium, each K(+) current exhibits a specific postnatal development, suggesting that regulatory factors taking place during development are major determinants of the functional role of K(+) channels in cardiac repolarization. The mouse atrium is, therefore, a very interesting model to gain information on the mechanisms regulating K(+) channel activity.
Trépanier-Boulay
Véronique
V
Research Center, Montreal Heart Institute, 5000 Rue Belanger est, Montréal, Québec, Canada H1T 1C8.
Lupien
Marie-Andrée
MA
St-Michel
Chantale
C
Fiset
Céline
C
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D005786:Gene Expression Regulation; D006321:Heart / Q000254:growth & development*; D006325:Heart Atria; D051379:Mice; D008815:Mice, Inbred Strains; D032383:Myocytes, Cardiac / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D015221:Potassium Channels; D012333:RNA, Messenger