SUR, ABC proteins targeted by KATP channel openers.
The sulfonylurea receptor SUR is an ATP binding cassette (ABC) protein of the ABCC/MRP family. Unlike other ABC proteins, it has no intrinsic transport function, neither active nor passive, but associates with the potassium channel proteins Kir6.1 or Kir6.2 to form the ATP-sensitive potassium (K(ATP)) channel. Within the channel complex SUR serves as a regulatory subunit which fine-tunes the gating of Kir6.x in response to alterations in cellular metabolism. It constitutes a major pharmaceutical target as it binds numerous drugs, K(ATP) channel openers and blockers, capable of up- or down-regulating channel activity. We here review current knowledge on the molecular basis of the interaction of classical K(ATP) channel openers (cromakalim, pinacidil, diazoxide) with SUR.
Moreau
Christophe
C
Biophysique Moléculaire and Cellulaire, CNRS UMR5090, CEA/DRDC, 17, Grenoble, France.
Prost
Anne-Lise
AL
Dérand
Renaud
R
Vivaudou
Michel
M
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D019806:Cromakalim / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D054086:KATP Channels; D008954:Models, Biological; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011955:Receptors, Drug / Q000737:chemistry* / Q000502:physiology*; D064233:Sulfonylurea Receptors; D015854:Up-Regulation; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate; D019806:Cromakalim; D003981:Diazoxide; D054086:KATP Channels; D020110:Pinacidil; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D020033:Protein Isoforms; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C092520:uK-ATP-1 potassium channel