KATP-channels in beta-cells in tissue slices are directly modulated by millimolar ATP

Mol Cell Endocrinol. 2005 Jan 31;230(1-2):51-8. doi: 10.1016/j.mce.2004.11.002.

Abstract

In pancreatic beta-cells, inhibition of K(ATP)-channels plays a pivotal role in signal transduction of glucose-induced insulin release. However, the extreme sensitivity of K(ATP)-channels to its ligand ATP as found in inside-out patches is not directly compatible with modulation of these channels at physiological [ATP](i). We studied K(ATP)-channel sensitivity to ATP in beta-cells in dispersed culture and in fresh pancreatic tissue slices. Physiological [ATP](i) blocks more than 99% of K(ATP)-channels in cultured beta-cells, while only 90% in beta-cells in slices, indicating reduced sensitivity to ATP in the fresh slices. Applying cytosolic factors like ADP, phosphatidylinositol-4,5-bisphosphate (PIP(2)) or oleoyl-CoA did not restore the K(ATP)-channel sensitivity in cultured beta-cells. Our data suggest that interaction between SUR1 and Kir6.2 subunit of the K(ATP)-channel could be a factor in sensitivity modulation. Tissue slices are the first beta-cell preparation to study direct K(ATP)-channel modulation by physiological [ATP](i).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Cells, Cultured
  • Humans
  • Islets of Langerhans / drug effects*
  • Male
  • Mice
  • Potassium Channels, Inwardly Rectifying / antagonists & inhibitors*
  • Tissue Culture Techniques

Substances

  • Potassium Channels, Inwardly Rectifying
  • Adenosine Triphosphate