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Channels (Austin). 2012 Nov-Dec;6(6):438-42. doi: 10.4161/chan.22209. Epub 2012 Sep 18.

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

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Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Wuhan, China.


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.

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