Inhibition of Kv1.3 channels by H-89 (N--[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) independent of protein kinase A

Biochem Pharmacol. 2001 Apr 15;61(8):1029-32. doi: 10.1016/s0006-2952(01)00556-1.


The effects of H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide), a potent and selective inhibitor of protein kinase A (PKA), were examined on Kv1.3 channels stably expressed in Chinese hamster ovary (CHO) cells using the patch clamp technique. In whole-cell recordings, H-89 decreased Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an IC(50) value of 1.70 microM. These effects were completely reversible after washout. Intracellular infusion with PKA inhibitors, adenosine 3', 5'-cyclic phosphorothioate-Rp (Rp-cAMPS) or protein kinase A inhibitor 5-24 (PKI 5-24) had no effect on Kv1.3 currents and did not prevent the inhibitory action of H-89 on the current. H-89 applied to the cytoplasmic surface also inhibited Kv1.3 currents in excised inside-out patches. These findings suggest that H-89 inhibits Kv1.3 currents independently of PKA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Isoquinolines / pharmacology*
  • Kv1.3 Potassium Channel
  • Potassium Channel Blockers*
  • Potassium Channels / metabolism
  • Potassium Channels, Voltage-Gated*
  • Sulfonamides*


  • Enzyme Inhibitors
  • Isoquinolines
  • Kv1.3 Potassium Channel
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Sulfonamides
  • Cyclic AMP-Dependent Protein Kinases
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide