Promiscuous coupling between the sulphonylurea receptor and inwardly rectifying potassium channels.
Sulphonylureas are a class of drugs widely used to treat non-insulin-dependent diabetes mellitus. These drugs act by binding to a sulphonylurea receptor (SUR) in the pancreatic beta-cell membrane which inhibits an ATP-sensitive potassium (K-ATP) channel and thereby stimulates insulin secretion. There has been much debate as to whether SUR and the K-ATP channel are the same or separate proteins, whether SUR confers ATP-sensitivity on an ATP-insensitive pore-forming subunit, and whether sulphonylureas can also modulate other types of K-channel. We show here that SUR itself does not possess intrinsic channel activity but that it endows sulphonylurea sensitivity on several types of inwardly-rectifying K-channels. It does not necessarily confer ATP-sensitivity on these channels.
Ammälä
C
C
University Laboratory of Physiology, Oxford, UK.
Moorhouse
A
A
Gribble
F
F
Ashfield
R
R
Proks
P
P
Smith
P A
PA
Sakura
H
H
Coles
B
B
Ashcroft
S J
SJ
Ashcroft
F M
FM
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D005905:Glyburide / Q000378:metabolism; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000378:metabolism*; D064233:Sulfonylurea Receptors; D014981:Xenopus
D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D011994:Recombinant Proteins; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate; D005905:Glyburide