Developmental changes in expression and biophysics of ion channels in the canine ventricle

Background: Developmental changes in the electrical characteristics of the ventricular myocardium are not well defined. This study examines the contribution of inwardly rectifying K+ current (I-K1), transient outward K+ current (I-to), delayed rectifier K+ currents (I-Kr and I-Ks) and sodium channel current (I-Na) to repolarization in the canine neonate myocardium. Methods: Single myocytes isolated from the left ventricle of 2-3 week old canine neonate hearts were studied using patch-clamp techniques. Results: Neonate cells were -6-fold smaller than those of adults (28.8 +/- 8.8 vs. 176 +/- 6.7 pF). I-K1 was larger in neonate myocytes and displayed a substantial inward component and an outward component with negative slope conductance, peaking at -60 mV (4.13 pA/pF). I-Kr tail currents (at -40 mV), were small (<20 pA). I-Ks could not be detected, even after exposure to isoproterenol (100 nM). I-to was also absent in the neonate, consistent with the absence of a phase 1 in the action potential. Peak I-Na, late I-Na and I-Ca were smaller in the neonate compared with adults. KCND3, KCNIP2 and KCNQ1 mRNA expression was half, while KCNH2 was equal and KCNJ2 was greater in the neonate when compared with adults. Conclusions: Two major repolarizing K+ currents (I-Ks and I-to) present in adult ventricular cells are absent in the 2 week old neonate. Peak and late I-Na are significantly smaller in the neonate. Our results suggest that the absence of these two currents in the neonate heart may increase the susceptibility to arrhythmias under certain long QT conditions. (C) 2013 Elsevier Ltd. All rights reserved.