Direct blockade of both cloned rat rod photoreceptor cyclic nucleotide-gated non-selective cation (CNG) channel alpha-subunit and native CNG channels from Xenopus rod outer segments by H-8, a non-specific cyclic nucleotide-dependent protein kinase inhibitor

Neurosci Lett. 1997 Sep 12;233(1):37-40. doi: 10.1016/s0304-3940(97)00622-8.


Using excised inside-out patch techniques, a non-specific cyclic nucleotide-dependent protein kinase inhibitor, H-8 (N-2-(methylamino)ethyl-5-isoquinolinesulfonamide), has been shown to suppress directly the activities of both rat rod photoreceptor cyclic GMP-gated channel alpha-subunits expressed in Xenopus oocytes and native cGMP-gated channels from Xenopus rod outer segments. When co-applied with 100 microM cGMP on the cytoplasmic side of the patches, current suppression by H-8 increased with membrane depolarization. Blockade by H-8 was not relieved by supersaturating concentrations of cGMP (1 mM). In addition, blockade by H-8 showed significant inhibition of channel activity at negative holding potentials when acting from the extracellular side of the channel. The results were consistent with the conclusion that H-8 can act as an open channel blocker from either side of the channel. Even though H-8 is a much more effective kinase inhibitor, it is frequently used at concentrations that cause inhibition of cGMP-gated channels and this effect needs to be taken into account when evaluating results obtained with this compound.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cations / metabolism
  • Cloning, Molecular
  • Cyclin-Dependent Kinases / drug effects*
  • Enzyme Inhibitors / pharmacology*
  • Ion Channels / drug effects*
  • Isoquinolines / pharmacology*
  • Oocytes / drug effects
  • Rats
  • Retinal Rod Photoreceptor Cells / drug effects*
  • Xenopus


  • Cations
  • Enzyme Inhibitors
  • Ion Channels
  • Isoquinolines
  • Cyclin-Dependent Kinases