title: Is ZD7288 a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channel currents?
abstract: 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.
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Wuhan, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wu
authors.forename: Liping
authors.initials: L
authors.lastname: Liao
authors.forename: Xiangming
authors.initials: X
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Luo
authors.forename: Tianming
authors.initials: T
authors.lastname: Yang
authors.forename: Chenhong
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology; D062553:NAV1.4 Voltage-Gated Sodium Channel / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D062553:NAV1.4 Voltage-Gated Sodium Channel; D011743:Pyrimidines; D011994:Recombinant Proteins; D015222:Sodium Channels; C082246:ICI D2788; D008012:Lidocaine