Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea-sensitive but ATP-insensitive K+ channel.
1. We analysed the K+ channel composed of the sulphonylurea receptor 2B (SUR2B) and an inwardly rectifying K+ channel subunit Kir6.1 coexpressed in a mammalian cell line, HEK293T, with the patch clamp technique. 2. In the cell-attached configuration, K+ channel openers (pinacidil and nicorandil) activated approximately 33 pS K+ channels (approximately 145 mM external K+), which were inhibited by the sulphonylurea glibenclamide. 3. Although SUR2B forms an ATP-sensitive K+ channel with Kir6.2, whose amino acid sequence is approximately 70% homologous with that of Kir6.1, the K+ channel composed of SUR2B and Kir6.1 surprisingly did not spontaneously open on patch excision in the absence of intracellular ATP. 4. In inside-out patches, uridine diphosphate and guanosine diphosphate induced channel activity, which was inhibited by glibenclamide but not ATP. Intracellular ATP on its own activated the channels. K+ channel openers and intracellular nucleotides synergistically activated the channel. 5. Therefore, the K+ channel composed of SUR2B and Kir6.1 is not a classical ATP-sensitive K+ channel but closely resembles the nucleotide diphosphate-dependent K+ channel in vascular smooth muscle cells.
Yamada
M
M
Department of Pharmacology II, Faculty of Medicine, Osaka University, Japan.
Isomoto
S
S
Matsumoto
S
S
Kondo
C
C
Shindo
T
T
Horio
Y
Y
Kurachi
Y
Y
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003001:Cloning, Molecular; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D054086:KATP Channels; D046911:Macromolecular Substances; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D018408:Patch-Clamp Techniques; D020110:Pinacidil; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000378:metabolism*; D013453:Sulfonylurea Compounds / Q000378:metabolism*; D064233:Sulfonylurea Receptors; D014530:Uridine Diphosphate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; C577511:Abcc9 protein, mouse; D006146:Guanidines; D007004:Hypoglycemic Agents; D054086:KATP Channels; D046911:Macromolecular Substances; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D014665:Vasodilator Agents; C092520:uK-ATP-1 potassium channel; D006153:Guanosine Diphosphate; D009536:Niacinamide; D020108:Nicorandil; D014530:Uridine Diphosphate; D020110:Pinacidil; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D008274:Magnesium; D005905:Glyburide