A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels

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 beta 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.