A Family of Sulfonylurea Receptors Determines the Pharmacological Properties of ATP-Sensitive K + Channels

• Published in: Neuron (Cambridge, Mass.) Mass.), 1996-05, Vol.16 (5), p.1011-1017
• Main Authors: Inagaki, Nobuya, Gonoi, Tohru, Iv, John P.Clement, Wang, Chang-Zheng, Aguilar-Bryan, Lydia, Bryan, Joseph, Seino, Susumu
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - physiology; Amino Acid Sequence; Animals; ATP-Binding Cassette Transporters - physiology; Cloning, Molecular; Gene Expression; Molecular Sequence Data; Potassium Channels - physiology; Potassium Channels, Inwardly Rectifying; Rats; Receptors, Drug - physiology; Recombinant Proteins; RNA, Messenger - genetics; Sequence Alignment; Sequence Homology, Amino Acid; Signal Transduction; Sulfonylurea Receptors; Tissue Distribution
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)80124-5

We have cloned an isoform of the sulfonylurea receptor (SUR), designated SUR2. Coexpression of SUR2 and the inward rectifier K + channel subunit Kir6.2 in COS1 cells reconstitutes the properties of K ATP channels described in cardiac and skeletal muscle. The SUR2/Kir6.2 channel is less sensitive than the SUR/Kir6.2 channel (the pancreatic β cell K ATP channel) to both ATP and the sulfonylurea glibenclamide and is activated by the cardiac K ATP channel openers, cromakalim and pinacidil, but not by diazoxide. In addition, SUR2 binds glibenclamide with lower affinity. The present study shows that the ATP sensitivity and pharmacological properties of K ATP channels are determined by a family of structurally related but functionally distinct sulfonylurea receptors.