WIN 17317-3 blocks Ca2+-activated K+ channels and enhances motility of guinea-pig detrusor muscle

Eur J Pharmacol. 2001 Sep 28;428(1):45-9. doi: 10.1016/s0014-2999(01)01347-4.

Abstract

Patch-clamp experiments in both clonal GH3 cells and guinea-pig bladder myocytes reveal that 1-benzyl-7-chloro-4-(n-pentylimino)-1,4-dihydroquinoline hydrochloride (WIN 17317-3), a potent blocker of Kv1.3 channels and potential immunomodulator, reduces, in a reversible manner and at low micromolar concentrations, K+ currents through Ca2+-activated high conductance K+ channels (BK channels). Blockade of BK channels is thought to account for the stimulatory effect of WIN 17317-3 on the contractility of guinea-pig bladder. This effect is not modified by tetrodotoxin (1 microM), but is abolished by nifedipine (0.1 microM). In conclusion. WIN 17317-3 lacks selectivity for the Kv1.3 channels, its postulated target for immunosuppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects*
  • Cell Separation
  • Cells, Cultured
  • Electric Stimulation
  • Electrophysiology
  • Guinea Pigs
  • In Vitro Techniques
  • Isometric Contraction / drug effects
  • Kv1.3 Potassium Channel
  • Muscle, Smooth / cytology
  • Muscle, Smooth / drug effects*
  • Patch-Clamp Techniques
  • Potassium Channel Blockers*
  • Potassium Channels*
  • Potassium Channels, Voltage-Gated*
  • Quinolines / pharmacology*
  • Urinary Bladder / drug effects

Substances

  • Kv1.3 Potassium Channel
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Quinolines
  • WIN 17317-3