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Br J Pharmacol
2001 Mar 01;1325:973-82. doi: 10.1038/sj.bjp.0703916.
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Interaction of stilbene disulphonates with cloned K(ATP) channels.
Proks P
,
Jones P
,
Ashcroft FM
.
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In this study, we tested the effects of the stilbene disulphonates DIDS and SITS on three different types of cloned K(ATP) channel (Kir6.2/SUR1, Kir6.2/SUR2A and Kir6.2DeltaC) heterologously expressed in Xenopus oocytes, with the aim of identifying the part of the channel which is involved in mediating disulphonate inhibition. We found that the inhibitory site(s) for these drugs lies within the Kir6.2 subunit of the channel, although its properties are further modulated by the sulphonylurea (SUR) subunit. In particular, SUR2A reduces both the rate and extent of block, by impairing the ability of DIDS binding to produce channel closure. The disulphonate-binding site interacts with the ATP inhibitory site on Kir6.2 because ATP is able to protect against irreversible channel inhibition by disulphonates. This effect is not mimicked by tolbutamide (at a concentration that interacts with Kir6.2) and is abolished by mutations that render the channel ATP insensitive. A number of point mutations in both the N and C termini of Kir6.2 reduced the extent and reversibility of channel inhibition by SITS. The results are consistent with the idea that residue C42 of Kir6.2 is likely to be involved in covalently linking of SITS to the channel. Other types of Kir channel (Kir1.1, Kir2.1 and Kir4.1) were also irreversibly blocked by DIDS, suggesting that these channels may share common binding sites for these stilbene disulphonates.
Aguilar-Bryan,
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
1995, Pubmed
Aguilar-Bryan,
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
1995,
Pubmed
Aguilar-Bryan,
Molecular biology of adenosine triphosphate-sensitive potassium channels.
1999,
Pubmed
Ashcroft,
Correlating structure and function in ATP-sensitive K+ channels.
1998,
Pubmed
Ashcroft,
ATP-sensitive K+ channels and insulin secretion: their role in health and disease.
1999,
Pubmed
Cabantchik,
The nature of the membrane sites controlling anion permeability of human red blood cells as determined by studies with disulfonic stilbene derivatives.
1972,
Pubmed
Clement,
Association and stoichiometry of K(ATP) channel subunits.
1997,
Pubmed
Drain,
KATP channel inhibition by ATP requires distinct functional domains of the cytoplasmic C terminus of the pore-forming subunit.
1998,
Pubmed
,
Xenbase
Furukawa,
Stilbene disulfonates block ATP-sensitive K+ channels in guinea pig ventricular myocytes.
1993,
Pubmed
Gatto,
Chemical modification with dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonate reveals the distance between K480 and K501 in the ATP-binding domain of the Na,K-ATPase.
1997,
Pubmed
Gribble,
Properties of cloned ATP-sensitive K+ currents expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Gribble,
The interaction of nucleotides with the tolbutamide block of cloned ATP-sensitive K+ channel currents expressed in Xenopus oocytes: a reinterpretation.
1997,
Pubmed
,
Xenbase
Inagaki,
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
1995,
Pubmed
Inagaki,
A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels.
1996,
Pubmed
Inagaki,
Subunit stoichiometry of the pancreatic beta-cell ATP-sensitive K+ channel.
1997,
Pubmed
Kozlowski,
ATP-sensitive K(+)-channel run-down is Mg2+ dependent.
1990,
Pubmed
Nichols,
Adenosine diphosphate as an intracellular regulator of insulin secretion.
1996,
Pubmed
Ohno-Shosaku,
Dual effects of ATP on K+ currents of mouse pancreatic beta-cells.
1987,
Pubmed
Reimann,
The role of lysine 185 in the kir6.2 subunit of the ATP-sensitive channel in channel inhibition by ATP.
1999,
Pubmed
,
Xenbase
Sakura,
Cloning and functional expression of the cDNA encoding a novel ATP-sensitive potassium channel subunit expressed in pancreatic beta-cells, brain, heart and skeletal muscle.
1995,
Pubmed
Shyng,
Regulation of KATP channel activity by diazoxide and MgADP. Distinct functions of the two nucleotide binding folds of the sulfonylurea receptor.
1997,
Pubmed
Shyng,
Octameric stoichiometry of the KATP channel complex.
1997,
Pubmed
Tanabe,
Direct photoaffinity labeling of the Kir6.2 subunit of the ATP-sensitive K+ channel by 8-azido-ATP.
1999,
Pubmed
,
Xenbase
Trapp,
Mechanism of ATP-sensitive K channel inhibition by sulfhydryl modification.
1998,
Pubmed
,
Xenbase
Trapp,
Molecular analysis of ATP-sensitive K channel gating and implications for channel inhibition by ATP.
1998,
Pubmed
,
Xenbase
Tucker,
Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor.
1997,
Pubmed
,
Xenbase
Tucker,
Molecular determinants of KATP channel inhibition by ATP.
1998,
Pubmed
,
Xenbase
Tucker,
Mapping of the physical interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2.
1999,
Pubmed
Zerangue,
A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels.
1999,
Pubmed
,
Xenbase
