Indeed, in rats with spontaneous AF one of the most upregulated genes was HCN4, encoding for proteins of If (Scridon et al., 2014), whereas in vitro studies performed in canine AF models have shown a significant increase in If activity and spontaneous diastolic depolarization rate, which were both counteracted by the If blocker ivabradine (Li et al., 2015). The gene discussed is HCN4; the disease is atrial fibrillation.