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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic Nucleotide-Gated Cation Channels / antagonists & inhibitors*
  • Cyclic Nucleotide-Gated Cation Channels / metabolism
  • Ganglia, Spinal / cytology
  • HEK293 Cells
  • Humans
  • Ion Channel Gating / drug effects*
  • Lidocaine / pharmacology
  • NAV1.4 Voltage-Gated Sodium Channel / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / metabolism
  • Sodium Channels / metabolism

Substances

  • Cyclic Nucleotide-Gated Cation Channels
  • NAV1.4 Voltage-Gated Sodium Channel
  • Pyrimidines
  • Recombinant Proteins
  • Sodium Channels
  • ICI D2788
  • Lidocaine