Characterisation of sulphonylurea and ATP-regulated K+ channels in rat pancreatic A-cells

Pflugers Arch. 1999 Sep;438(4):428-36. doi: 10.1007/s004249900076.

Abstract

We have monitored whole-cell and single channel ATP-sensitive K+ (KATP) currents in isolated rat glucagon-secreting pancreatic A-cells. Tolbutamide produced a concentration-dependent decrease in the whole-cell KATP conductance (Ki = 6 microM) and initiated action potential firing. The K+ channel opener diazoxide, but not cromakalim or pinacidil, inhibited electrical activity and increased the whole-cell K+ conductance fourfold. ATP applied to the intracellular face of the membrane inhibited KATP channel activity with a Ki of 17 microM, an effect that could be counteracted by Mg-ADP and Mg-GDP. GTP and UTP did not affect KATP channel activity. Phosphatidylinositol 4,5-bisphosphate activated KATP channels inhibited by ATP after a delay of 90 s. In situ hybridisation demonstrated the expression of the mRNA encoding KATP channel subunits Kir6.2 and SUR1 but not Kir6.1 and SUR2. We conclude that rat pancreatic A-cells express KATP channels with the nucleotide-, sulphonylurea- and K+ channel-opener sensitivities expected for a channel formed by Kir6.2 and SUR1 subunits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Adenosine Diphosphate / pharmacology
  • Adenosine Triphosphate / antagonists & inhibitors
  • Adenosine Triphosphate / pharmacology
  • Adenosine Triphosphate / physiology*
  • Animals
  • Electrophysiology
  • Guanosine Diphosphate / pharmacology
  • Guanosine Triphosphate / pharmacology
  • Hypoglycemic Agents / pharmacology
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Male
  • Membrane Potentials / drug effects
  • Phosphatidylinositol 4,5-Diphosphate / pharmacology
  • Potassium Channel Blockers
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • Rats
  • Rats, Inbred Lew
  • Receptors, Drug / metabolism
  • Sulfonylurea Compounds / metabolism*
  • Sulfonylurea Receptors
  • Tolbutamide / pharmacology
  • Uridine Triphosphate / pharmacology

Substances

  • ATP-Binding Cassette Transporters
  • Abcc8 protein, rat
  • Abcc9 protein, rat
  • Hypoglycemic Agents
  • Phosphatidylinositol 4,5-Diphosphate
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Compounds
  • Sulfonylurea Receptors
  • Guanosine Diphosphate
  • Adenosine Diphosphate
  • Guanosine Triphosphate
  • Adenosine Triphosphate
  • Tolbutamide
  • Uridine Triphosphate