We investigated the effects of chronic and moderate heart rate (HR) reduction on ion channel expression in the mouse sinoatrial node (SAN) and ventricle. Ten-week old male C57BL/6 mice were treated twice daily with either vehicle or ivabradine 5 mg/kg given orally during 3 weeks. The effects of HR reduction on cardiac electrical activity were investigated in anesthetized mice with serial ECGs and in freely-moving mice with telemetric recordings. Using high-throughput real time RT-PCR, the expression of 68 ion channel subunits was evaluated in the SAN and ventricle at the end of the treatment period. In conscious mice, ivabradine induced a mean 16% HR reduction over a 24-hour period that was sustained over the 3-week administration. Other ECG parameters were not modified. Two-way hierarchical clustering analysis of gene expression revealed a separation of ventricles from SANs but no discrimination between treated and untreated ventricles indicating that HR reduction per se induced limited remodeling in this tissue. In contrast, SAN samples clustered in two groups depending on the treatment. In the SAN from ivabradine-treated mice, the expression of 9 ion channel subunits, including Nav1 (-25%), Cav3.1 (-29%), Kir6.1 (-28%), Kv2 (-41%) and Kv3 (-30%), was significantly decreased. Eight genes were significantly up-regulated, including K⁺ channel -subunits (Kv1.1, +30%; Kir2.1, +29%; Kir3.1, +41%), hyperpolarization-activated cation channels (HCN2, +24%; HCN4, +52%) and connexin 43 (+26%). We conclude that reducing HR induces a complex remodeling of ion channel expression in the SAN but has little impact on ion channel transcripts in the ventricle.