Developmental Changes in Potassium Channel Expression in the Canine Heart: Implications for Sudden Infant Death Caused by Arrhythmias

Background and Rationale: It is believed that at least 10% of Sudden Infant Death syndrome cases are due to cardiac arrhythmia, however, developmental changes in the electrophysiological characteristics are not well defined in the higher mammalian heart. The present study examines the contribution of the inwardly rectifying K+ current (IK1), the transient outward K+ current (Ito) and the delayed rectifier K+ currents (IKr and IKs) to repolarization in the canine neonate myocardium.Methods and Results: Single cells were obtained from 2-3 week old canine neonate hearts subjected to enzymatic dispersion. Ventricular cells were isolated from both the left and right ventricles. Compared with adult ventricular cells, the size of neonate ventricular cells were approximately 6 times smaller. Action potential recordings showed a lack of phase 1 repolarization in neonatal myocytes. Accordingly, voltage clamp studies showed no Ito in neonatal myocytes. The inwardly rectifying potassium current IK1 was similar between neonate and adult. Measurement of the delayed rectifier(s) showed the presence of IKr, but not IKs. Additionally, mRNA levels for KCNQ1, KChIP2 and Kv4.3 were more than 2-fold lower in the neonatal heart compared with the adult heart;however, KCNH2 expression was unchanged.Conclusion: Repolarization in 2-3 week old canine neonate ventricle is due mainly to the presence of IK1 and IKr. Neither IKs nor Ito were recorded at this stage of development. These findings point to a reduced repolarization reserve in ventricular myocytes isolated from canine neonatal hearts when compared to those of adults. Our data may help explain why infants are more vulnerable to developing QT prolongation and arrhythmias.