Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
1. ATP-sensitive potassium (KATP) channels are composed of pore-forming Kir6.2 and regulatory SUR subunits. A truncated isoform of Kir6.2, Kir6.2DeltaC26, expresses ATP-sensitive channels in the absence of SUR1, suggesting the ATP-inhibitory site lies on the Kir6. 2 subunit. 2. We examined the effect on the channel ATP sensitivity of mutating the arginine residue at position 50 (R50) in the N-terminus of Kir6.2, by recording macroscopic currents in membrane patches excised from Xenopus oocytes expressing wild-type or mutant Kir6.2DeltaC26. 3. Substitution of R50 by serine, alanine or glycine reduced the Ki for ATP inhibition from 117 microM to 800 microM, 1.1 mM and 3.8 mM, respectively. The single-channel conductance and kinetics were unaffected by any of these mutations. Mutation to glutamate, lysine, asparagine, glutamine or leucine had a smaller effect (Ki, approximately 300-400 microM). The results indicate that the side chain of the arginine residue at position 50 is unlikely to contribute directly to the binding site for ATP, and suggest it may affect ATP inhibition by allosteric interactions. 4. Mutation of the isoleucine residue at position 49 to glycine (I49G) reduced the channel ATP sensitivity, while the mutation of the glutamate residue at position 51 to glycine (E51G) did not. 5. When a mutation in the N-terminus of Kir6.2DeltaC26 that alters ATP sensitivity (R50S; Ki, 800 microM) was combined with one in the C-terminus (E179Q; Ki, 300 microM), the Ki for the apparent ATP sensitivity was increased to 2.8 mM. The Hill coefficient was also increased. This suggests that the N- and C-termini of Kir6.2 may co-operate to influence channel closure by ATP.
Ashcroft,
Electrophysiology of the pancreatic beta-cell.
1989, Pubmed
Ashcroft,
Electrophysiology of the pancreatic beta-cell.
1989,
Pubmed Ashcroft,
Properties and functions of ATP-sensitive K-channels.
1990,
Pubmed Clement,
Association and stoichiometry of K(ATP) channel subunits.
1997,
Pubmed Gordon,
Localization of regions affecting an allosteric transition in cyclic nucleotide-activated channels.
1995,
Pubmed
,
Xenbase Gribble,
Properties of cloned ATP-sensitive K+ currents expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase Huang,
Binding of the G protein betagamma subunit to multiple regions of G protein-gated inward-rectifying K+ channels.
1997,
Pubmed Huang,
Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation.
1995,
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 Isomoto,
A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel.
1996,
Pubmed Jackson,
Successive openings of the same acetylcholine receptor channel are correlated in open time.
1983,
Pubmed Kyte,
A simple method for displaying the hydropathic character of a protein.
1982,
Pubmed Pascual,
Contribution of the NH2 terminus of Kv2.1 to channel activation.
1997,
Pubmed Proks,
Phentolamine block of KATP channels is mediated by Kir6.2.
1997,
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,
Control of rectification and gating of cloned KATP channels by the Kir6.2 subunit.
1997,
Pubmed 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 Varnum,
Interdomain interactions underlying activation of cyclic nucleotide-gated channels.
1997,
Pubmed
,
Xenbase
