Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor.
ATP-sensitive potassium channels (K-ATP channels) couple cell metabolism to electrical activity and are important in the physiology and pathophysiology of many tissues. In pancreatic beta-cells, K-ATP channels link changes in blood glucose concentration to insulin secretion. They are also the target for clinically important drugs such as sulphonylureas, which stimulate secretion, and the K+ channel opener diazoxide, which inhibits insulin release. Metabolic regulation of K-ATP channels is mediated by changes in intracellular ATP and Mg-ADP levels, which inhibit and activate the channel, respectively. The beta-cell K-ATP channel is a complex of two proteins: an inward-rectifier K+ channel subunit, Kir6.2, and the sulphonylurea receptor, SUR1. We show here that the primary site at which ATP acts to mediate K-ATP channel inhibition is located on Kir6.2, and that SUR1 is required for sensitivity to sulphonylureas and diazoxide and for activation by Mg-ADP.
Tucker
S J
SJ
University Laboratory of Physiology, Oxford, UK.
Gribble
F M
FM
Zhao
C
C
Trapp
S
S
Ashcroft
F M
FM
D018528:ATP-Binding Cassette Transporters; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D008969:Molecular Sequence Data; D009865:Oocytes; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000737:chemistry / Q000378:metabolism*; D017384:Sequence Deletion; D013453:Sulfonylurea Compounds / Q000378:metabolism; D064233:Sulfonylurea Receptors; D014044:Tolbutamide / Q000494:pharmacology; D014981:Xenopus
D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D003981:Diazoxide