title: KATP-channels in beta-cells in tissue slices are directly modulated by millimolar ATP.
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).
authors.affiliation: European Neuroscience Institute Göttingen, Waldweg 33, 37073 Göttingen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Speier
authors.forename: S-B
authors.initials: SB
authors.lastname: Yang
authors.forename: K
authors.initials: K
authors.lastname: Sroka
authors.forename: T
authors.initials: T
authors.lastname: Rose
authors.forename: M
authors.initials: M
authors.lastname: Rupnik
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D051379:Mice; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors*; D046509:Tissue Culture Techniques
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D000255:Adenosine Triphosphate