: Metabolic inhibition impairs ATP-sensitive K+ channel block by sulfonylurea in pancreatic beta-cells.

  • Mukai, E., Ishida, H., Kato, S., Tsuura, Y., Fujimoto, S., Ishida-Takahashi, A., Horie, M., Tsuda, K. and Seino Y
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The effect of metabolic inhibition on the blocking of beta-cell ATP-sensitive K+ channels (KATP channels) by glibenclamide was investigated using a patch-clamp technique. Inhibition of KATP channels by glibenclamide was attenuated in the cell-attached mode under metabolic inhibition induced by 2,4-dinitrophenol. Under a low concentration (0.1 microM) of ATP applied in the inside-out mode, KATP channel activity was not fully abolished, even when a high dose of glibenclamide was applied, in contrast to the dose-dependent and complete KATP channel inhibition under 10 microM ATP. On the other hand, cibenzoline, a class Ia antiarrhythmic agent, inhibits KATP channel activity in a dose-dependent manner and completely blocks it, even under metabolic inhibition. In sulfonylurea receptor (SUR1)- and inward rectifier K+ channel (Kir6.2)-expressed proteins, cibenzoline binds directly to Kir6.2, unlike glibenclamide. Thus, KATP channel inhibition by glibenclamide is impaired under the condition of decreased intracellular ATP in pancreatic beta-cells, probably because of a defect in signal transmission between SUR1 and Kir6.2 downstream of the site of sulfonylurea binding to SUR1.

Author-supplied keywords

  • 2
  • 4-Dinitrophenol
  • 4-Dinitrophenol: pharmacology
  • ATP-Binding Cassette Transporters
  • Adenosine Triphosphate
  • Adenosine Triphosphate: pharmacology
  • Animals
  • Anti-Arrhythmia Agents
  • Anti-Arrhythmia Agents: pharmacology
  • Cells
  • Cultured
  • Drug
  • Drug: drug effects
  • Drug: physiology
  • Glyburide
  • Glyburide: pharmacology
  • Imidazoles
  • Imidazoles: pharmacology
  • Inwardly Rectifying
  • Islets of Langerhans
  • Islets of Langerhans: drug effects
  • Islets of Langerhans: physiology
  • Male
  • Membrane Potentials
  • Membrane Potentials: drug effects
  • Membrane Potentials: physiology
  • Patch-Clamp Techniques
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels: drug effects
  • Potassium Channels: physiology
  • Rats
  • Receptors
  • Wistar

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  • Y: Mukai, E., Ishida, H., Kato, S., Tsuura, Y., Fujimoto, S., Ishida-Takahashi, A., Horie, M., Tsuda, K. and Seino

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