title: KATP channel inhibition by ATP requires distinct functional domains of the cytoplasmic C terminus of the pore-forming subunit.
abstract: ATP-sensitive potassium ("KATP") channels are rapidly inhibited by intracellular ATP. This inhibition plays a crucial role in the coupling of electrical activity to energy metabolism in a variety of cells. The KATP channel is formed from four each of a sulfonylurea receptor (SUR) regulatory subunit and an inwardly rectifying potassium (Kir6.2) pore-forming subunit. We used systematic chimeric and point mutagenesis, combined with patch-clamp recording, to investigate the molecular basis of ATP-dependent inhibition gating of mouse pancreatic beta cell KATP channels expressed in Xenopus oocytes. We identified distinct functional domains of the presumed cytoplasmic C-terminal segment of the Kir6.2 subunit that play an important role in this inhibition. Our results suggest that one domain is associated with inhibitory ATP binding and another with gate closure.
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104, USA. drain@mail.med.upenn.edu
authors.forename: P
authors.initials: P
authors.lastname: Drain
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D051379:Mice; D018408:Patch-Clamp Techniques; D018272:Porins / Q000737:chemistry / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000737:chemistry / Q000502:physiology*; D014981:Xenopus
chemical_list: D018272:Porins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate