Nature 379, 545 - 548 (08 February 1996); doi:10.1038/379545a0

Promiscuous coupling between the sulphonylurea receptor and inwardly rectifying potassium channels

Carlna Ämmälä^*, Andrew Moorhouse^*, Fiona Gribble^*, Rebecca Ashfleld^†, Peter Proks^*, Paul A. Smith^*, Hiroshl Sakura^*, Barbara Coles^*, Stephen J. H. Ashcroft^† & Frances M. Ashcroft^*‡

^* University Laboratory of Physiology, Parks Road Oxford, OX1 3PT, UK
^†Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
^‡To Whom correspondence should be addressed.

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 -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-sensithity 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 It-channels. It does not necessarily confer ATP-sensitivity on these channels.

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