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Pyridine nucleotide regulation of the KATP channel Kir6.2/SUR1 expressed in Xenopus oocytes.
Dabrowski M
,
Trapp S
,
Ashcroft FM
.
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The pancreatic beta-cell type of ATP-sensitive potassium (KATP) channel (Kir6.2/SUR1) is inhibited by intracellular ATP and ADP, which bind to the Kir6.2 subunit, and is activated by Mg-nucleotide interaction with the regulatory sulphonylurea receptor subunits (SUR1). The nicotinamide adenine dinucleotides NAD and NADP consist of an ADP molecule with a ribose group and a nicotinamide moiety attached to the terminal phosphate. Both these molecules block native KATP channels in pancreatic beta-cells at concentrations above 500 microM, and activate them at lower concentrations. We therefore investigated whether NAD and NADP interact with both Kir6.2 and SUR1 subunits of the KATP channel by comparing the potency of these agents on recombinant Kir6.2DeltaC and Kir6.2/SUR1 channels expressed in Xenopus oocytes. Our results show that, at physiological concentrations, NAD and NADP interact with the nucleotide inhibitory site of Kir6.2 to inhibit Kir6.2/SUR1 currents. They may therefore contribute to the resting level of channel inhibition in the intact cell. Importantly, our data also reveal that this interaction is dependent on the presence of SUR1, which may act by increasing the width of the nucleotide-binding pocket of Kir6.2.
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
Ashcroft,
Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells.
,
Pubmed
Ashcroft,
Electrophysiology of the pancreatic beta-cell.
1989,
Pubmed
Baukrowitz,
PIP2 and PIP as determinants for ATP inhibition of KATP channels.
1998,
Pubmed
,
Xenbase
Duchen,
Substrate-dependent changes in mitochondrial function, intracellular free calcium concentration and membrane channels in pancreatic beta-cells.
1993,
Pubmed
Dunne,
Effects of pyridine nucleotides on the gating of ATP-sensitive potassium channels in insulin-secreting cells.
1988,
Pubmed
Fan,
Anionic phospholipids activate ATP-sensitive potassium channels.
1997,
Pubmed
Gribble,
Properties of cloned ATP-sensitive K+ currents expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Gribble,
The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide.
1997,
Pubmed
,
Xenbase
Gribble,
MgATP activates the beta cell KATP channel by interaction with its SUR1 subunit.
1998,
Pubmed
,
Xenbase
Harding,
Modulation of three types of potassium selective channels by NAD and other pyridine nucleotides in human pancreatic beta-cells. NAD and K+ channels in human beta-cells.
1997,
Pubmed
Inagaki,
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
1995,
Pubmed
Matsuo,
Mutations in the linker domain of NBD2 of SUR inhibit transduction but not nucleotide binding.
2002,
Pubmed
,
Xenbase
Patterson,
Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet beta cells.
2000,
Pubmed
Pralong,
Single islet beta-cell stimulation by nutrients: relationship between pyridine nucleotides, cytosolic Ca2+ and secretion.
1990,
Pubmed
Rocheleau,
Pancreatic islet beta-cells transiently metabolize pyruvate.
2002,
Pubmed
Röper,
Metabolic inhibition and low internal ATP activate K-ATP channels in rat dopaminergic substantia nigra neurones.
1995,
Pubmed
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,
Membrane phospholipid control of nucleotide sensitivity of KATP channels.
1998,
Pubmed
Tanabe,
Direct photoaffinity labeling of the Kir6.2 subunit of the ATP-sensitive K+ channel by 8-azido-ATP.
1999,
Pubmed
,
Xenbase
Trapp,
Activation and inhibition of K-ATP currents by guanine nucleotides is mediated by different channel subunits.
1997,
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
Ueda,
Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide.
1999,
Pubmed
Zerangue,
A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels.
1999,
Pubmed
,
Xenbase
Zingman,
Signaling in channel/enzyme multimers: ATPase transitions in SUR module gate ATP-sensitive K+ conductance.
2001,
Pubmed
