Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea-sensitive but ATP-insensitive K+ channel

J Physiol. 1997 Mar 15;499 ( Pt 3)(Pt 3):715-20. doi: 10.1113/jphysiol.1997.sp021963.

Abstract

1. We analysed the K+ channel composed of the sulphonylurea receptor 2B (SUR2B) and an inwardly rectifying K+ channel subunit Kir6.1 coexpressed in a mammalian cell line, HEK293T, with the patch clamp technique. 2. In the cell-attached configuration, K+ channel openers (pinacidil and nicorandil) activated approximately 33 pS K+ channels (approximately 145 mM external K+), which were inhibited by the sulphonylurea glibenclamide. 3. Although SUR2B forms an ATP-sensitive K+ channel with Kir6.2, whose amino acid sequence is approximately 70% homologous with that of Kir6.1, the K+ channel composed of SUR2B and Kir6.1 surprisingly did not spontaneously open on patch excision in the absence of intracellular ATP. 4. In inside-out patches, uridine diphosphate and guanosine diphosphate induced channel activity, which was inhibited by glibenclamide but not ATP. Intracellular ATP on its own activated the channels. K+ channel openers and intracellular nucleotides synergistically activated the channel. 5. Therefore, the K+ channel composed of SUR2B and Kir6.1 is not a classical ATP-sensitive K+ channel but closely resembles the nucleotide diphosphate-dependent K+ channel in vascular smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Cloning, Molecular
  • Glyburide / pharmacology
  • Guanidines / pharmacology
  • Guanosine Diphosphate / pharmacology
  • Guanosine Triphosphate / pharmacology
  • Hypoglycemic Agents / pharmacology
  • KATP Channels
  • Macromolecular Substances
  • Magnesium / metabolism
  • Mice
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular / metabolism
  • Niacinamide / analogs & derivatives
  • Niacinamide / pharmacology
  • Nicorandil
  • Patch-Clamp Techniques
  • Pinacidil
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • Receptors, Drug / metabolism*
  • Sulfonylurea Compounds / metabolism*
  • Sulfonylurea Receptors
  • Uridine Diphosphate / pharmacology
  • Vasodilator Agents / pharmacology

Substances

  • ATP-Binding Cassette Transporters
  • Abcc9 protein, mouse
  • Guanidines
  • Hypoglycemic Agents
  • KATP Channels
  • Macromolecular Substances
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Compounds
  • Sulfonylurea Receptors
  • Vasodilator Agents
  • uK-ATP-1 potassium channel
  • Guanosine Diphosphate
  • Niacinamide
  • Nicorandil
  • Uridine Diphosphate
  • Pinacidil
  • Guanosine Triphosphate
  • Adenosine Triphosphate
  • Magnesium
  • Glyburide

Associated data

  • GENBANK/D88159