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 KATP 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.
Inagaki
N
N
Division of Molecular Medicine Center for Biomedical Science, Chiba University School of Medicine, Chuo-ku, Chiba 260, Japan.
Gonoi
T
T
Clement
J P
JP
Wang
C Z
CZ
Aguilar-Bryan
L
L
Bryan
J
J
Seino
S
S
D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000255:Adenosine Triphosphate / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D015870:Gene Expression; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011955:Receptors, Drug / Q000502:physiology*; D011994:Recombinant Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D064233:Sulfonylurea Receptors; D014018:Tissue Distribution
D018528:ATP-Binding Cassette Transporters; C577512:Abcc9 protein, rat; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D011955:Receptors, Drug; D011994:Recombinant Proteins; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate