Postnatal development of atrial repolarization in the mouse

Objectives and methods: 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-Kl) 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. Conclusion: 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. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.