Is ZD7288 a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channel currents?

ZD7288 has been widely used as a tool in the study of hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels), and to test the relationships between HCN channels and heart and brain function. ZD7288 is widely considered a selective blocker of HCN currents. Here we show that ZD7288 inhibits not only HCN channel currents, but also Na+ currents in DRG neurons and ZD7288 was confirmed to inhibit Na+ current in HEK293 cells transfected with Na(v)1.4 plasmids. Thus our findings challenge the view that ZD7288 is a selective blocker of HCN channels. Conclusions about the role of NCN channels in neuronal function should be re-evaluated if based exclusively on the effect of ZD7288.