Selective activation of Ca(2+)-dependent K+ channels by novel benzimidazolone

Eur J Pharmacol. 1994 Jan 4;251(1):53-9. doi: 10.1016/0014-2999(94)90442-1.

Abstract

Activators and blockers of specific ion channels are important pharmacological tools for characterizing ion channels and their influence on cell function. The large-conductance Ca(2+)-dependent K+ channel (BK channel) is blocked by peptides such as charybdotoxin and iberiotoxin, but no selective activator of the channel has been described. Here we report single-channel and whole-cell patch-clamp experiments on the specific activation of BK channels in aortic smooth muscle cells with a new heterocyclic molecule, NS 1619 (1-(2'-hydroxy-5'-trifluoromethylphenyl)-5-trifluoromethyl- 2(3H)benzimidazolone). The effect of NS 1619 on the BK channel was dose-dependent, resulting in a shift of the activation curve by up to -50 mV towards negative membrane potentials. The effect was fully reversible and was antagonized by charybdotoxin as well as by tetraethylammonium ions. The compound hyperpolarized the smooth muscle cells. NS 1619 is a selective and new type of K+ channel activator, which may significantly modulate cell excitability.

MeSH terms

  • Animals
  • Benzimidazoles / pharmacology*
  • Binding Sites / drug effects
  • Calcium / physiology*
  • Cattle
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Electrophysiology
  • Guinea Pigs
  • Humans
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Mice
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Potassium Channels / drug effects*
  • Rats
  • Tetraethylammonium Compounds / pharmacology

Substances

  • Benzimidazoles
  • Potassium Channels
  • Tetraethylammonium Compounds
  • NS 1619
  • Calcium