title: The molecular assembly of ATP-sensitive potassium channels. Determinants on the pore forming subunit.
abstract: ATP-sensitive potassium channels form a link between membrane excitability and cellular metabolism. These channels are important in physiological processes such as insulin release and they are an important site of drug action. They are an octomeric complex comprised of four sulfonylurea receptors, a member of the ATP-binding cassette family of proteins, and four Kir 6.0 subunits from the inward rectifier family of potassium channels. We have investigated the nature of the interaction between SUR1 and Kir 6.2 and the domains on the channel responsible for the biochemical and functional manifestations of coupling. The results point to the proximal C terminus determining biochemical interaction in a region that also largely governs homotypic and heterotypic interaction between different Kir family members. While this domain may be necessary for functional communication between the two proteins, it is not sufficient since relative modifications of either the N or C terminus are able to disrupt many aspects of functional coupling mediated by the sulfonylurea receptor.
authors.affiliation: Centre for Clinical Pharmacology, Department of Medicine, The Rayne Institute, University College, 5 University St., London WC1E 6JJ, United Kingdom.
authors.forename: J P
authors.initials: JP
authors.lastname: Giblin
authors.forename: J L
authors.initials: JL
authors.lastname: Leaney
authors.forename: A
authors.initials: A
authors.lastname: Tinker
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015640:Ion Channel Gating; D008954:Models, Biological; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011485:Protein Binding; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D064233:Sulfonylurea Receptors; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate; D014044:Tolbutamide