Block of pancreatic ATP-sensitive K+ channels and insulinotrophic action by the antiarrhythmic agent, cibenzoline

Ayako Ishida-Takahashi, Minoru Horie, Yoshiyuki Tsuura, Hitoshi Ishida, Tomohiko Ai, Shigetake Sasayama

Research output: Contribution to journalArticle

38 Scopus citations


1 We investigated the effect of cibenzoline (a class Ia antiarrhythmic drug) on basal insulin secretory activity of rat pancreatic islets and ATP-sensitive KATP channels (KATP) in single pancreatic βcells of the same species, using radioimmunoassay and patch clamp techniques. 2 Micromolar cibenzoline had a dose-dependent insulinotrophic action with an EC50 of 94.2 ± 46.4 μM. The compound inhibited the activity of the KATP channel recorded from a single β-cell in a concentration-dependent manner. The IC50 was 0.4 μM in the inside-out mode and 5.2 μM in the cell-attached mode, at pH 7.4. 3 In the cell-attached mode, alkalinization of extracellular solution increased the inhibitory action of cibenzoline and the IC50 was reduced from 26.8 μM at pH 6.2 to 0.9 μM at pH 8.4. On the other hand, the action of cibenzoline in the excised inside-out mode was acute in onset with a small IC50, indicating that the drug attains its binding site from the cytoplasmic side of the cell membrane. 4 In the inside-out mode, micromolar ADP reactivated the cibenzoline-blocked KATP channels in a manner similar to that by which ADP restored ATP-dependent block of the channel. 5 The binding of [3H]-glibenclamide to pancreatic islets was inhibited by glibenclamide but not by cibenzoline. In contrast, the [3H]-cibenzoline binding was displaced by unlabelled cibenzoline but not by glibenclamide. It is concluded that cibenzoline blocks pancreatic KATP channels via a binding site distinct from the sulphonylurea receptor.

Original languageEnglish (US)
Pages (from-to)1749-1755
Number of pages7
JournalBritish Journal of Pharmacology
Issue number8
StatePublished - 1996


  • ATP-sensitive K channel
  • Antiarrhythmic agent
  • Cibenzoline
  • Drug-induced hypoglycaemia
  • Pancreatic β cells

ASJC Scopus subject areas

  • Pharmacology

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