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.
Allosteric modulation of the mouse Kir6.2 channel by intracellular H+ and ATP.
Wu J
,
Cui N
,
Piao H
,
Wang Y
,
Xu H
,
Mao J
,
Jiang C
.
???displayArticle.abstract???
The ATP-sensitive K+ (K(ATP)) channels are regulated by intracellular H+ in addition to ATP, ADP, and phospholipids. Here we show evidence for the interaction of H+ with ATP in regulating a cloned K(ATP) channel, i.e. Kir6.2 expressed with and without the SUR1 subunit. Channel sensitivity to ATP decreases at acidic pH, while the pH sensitivity also drops in the presence of ATP. These effects are more evident in the presence of the SUR1 subunit. In the Kir6.2 + SUR1, the pH sensitivity is reduced by about 0.4 pH units with 100 microM ATP and 0.6 pH units with 1 mM ATP, while a decrease in pH from 7.4 to 6.8 lowers the ATP sensitivity by about fourfold. The Kir6.2 + SUR1 currents are strongly activated at pH 5.9-6.5 even in the presence of 1 mM ATP. The modulations appear to take place at His175 and Lys185 that are involved in proton and ATP sensing, respectively. Mutation of His175 completely eliminates the pH effect on the ATP sensitivity. Similarly, the K185E mutant-channel loses the ATP-dependent modulation of the pH sensitivity. Thus, allosteric modulations of the cloned K(ATP) channel by ATP and H+ are demonstrated. Such a regulation allows protons to activate directly the K(ATP) channels and release channel inhibition by intracellular ATP; the pH effect is further enhanced with a decrease in ATP concentration as seen in several pathophysiological conditions.
Allard,
Activation of ATP-dependent K+ channels by metabolic poisoning in adult mouse skeletal muscle: role of intracellular Mg(2+) and pH.
1995, Pubmed
Allard,
Activation of ATP-dependent K+ channels by metabolic poisoning in adult mouse skeletal muscle: role of intracellular Mg(2+) and pH.
1995,
Pubmed
Ashcroft,
Correlating structure and function in ATP-sensitive K+ channels.
1998,
Pubmed
Barry,
Liquid junction potentials and small cell effects in patch-clamp analysis.
1991,
Pubmed
Baukrowitz,
PIP2 and PIP as determinants for ATP inhibition of KATP channels.
1998,
Pubmed
,
Xenbase
Baukrowitz,
Inward rectification in KATP channels: a pH switch in the pore.
1999,
Pubmed
Cuevas,
Effect of H+ on ATP-regulated K+ channels in feline ventricular myocytes.
1991,
Pubmed
Davies,
Modulation of ATP-sensitive K+ channels in skeletal muscle by intracellular protons.
1990,
Pubmed
Davies,
The effect of intracellular pH on ATP-dependent potassium channels of frog skeletal muscle.
1992,
Pubmed
Drain,
KATP channel inhibition by ATP requires distinct functional domains of the cytoplasmic C terminus of the pore-forming subunit.
1998,
Pubmed
,
Xenbase
Fan,
Modulation of ATP-sensitive K+ channels by internal acidification in insulin-secreting cells.
1994,
Pubmed
Fan,
Anionic phospholipids activate ATP-sensitive potassium channels.
1997,
Pubmed
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
Koster,
ATP inhibition of KATP channels: control of nucleotide sensitivity by the N-terminal domain of the Kir6.2 subunit.
1999,
Pubmed
Koyano,
ATP-regulated K+ channels are modulated by intracellular H+ in guinea-pig ventricular cells.
1993,
Pubmed
Larsson,
Stimulation of the KATP channel by ADP and diazoxide requires nucleotide hydrolysis in mouse pancreatic beta-cells.
1993,
Pubmed
Lederer,
Nucleotide modulation of the activity of rat heart ATP-sensitive K+ channels in isolated membrane patches.
1989,
Pubmed
MONOD,
ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL.
1965,
Pubmed
MacGregor,
Nucleotides and phospholipids compete for binding to the C terminus of KATP channels.
2002,
Pubmed
Misler,
Modulation of gating of a metabolically regulated, ATP-dependent K+ channel by intracellular pH in B cells of the pancreatic islet.
1989,
Pubmed
Noma,
ATP-regulated K+ channels in cardiac muscle.
,
Pubmed
Piao,
Requirement of multiple protein domains and residues for gating K(ATP) channels by intracellular pH.
2001,
Pubmed
,
Xenbase
Proks,
Interaction of vanadate with the cloned beta cell K(ATP) channel.
1999,
Pubmed
,
Xenbase
Proks,
Effects of intracellular pH on ATP-sensitive K+ channels in mouse pancreatic beta-cells.
1994,
Pubmed
Proks,
Involvement of the N-terminus of Kir6.2 in the inhibition of the KATP channel by ATP.
1999,
Pubmed
,
Xenbase
Quayle,
ATP-sensitive and inwardly rectifying potassium channels in smooth muscle.
1997,
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
Shyng,
Control of rectification and gating of cloned KATP channels by the Kir6.2 subunit.
1997,
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,
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
Vivaudou,
Modification by protons of frog skeletal muscle KATP channels: effects on ion conduction and nucleotide inhibition.
1995,
Pubmed
Xu,
Direct activation of cloned K(atp) channels by intracellular acidosis.
2001,
Pubmed
,
Xenbase
Xu,
Distinct histidine residues control the acid-induced activation and inhibition of the cloned K(ATP) channel.
2001,
Pubmed
,
Xenbase
Yang,
Biophysical and molecular mechanisms underlying the modulation of heteromeric Kir4.1-Kir5.1 channels by CO2 and pH.
2000,
Pubmed
,
Xenbase
Yokoshiki,
ATP-sensitive K+ channels in pancreatic, cardiac, and vascular smooth muscle cells.
1998,
Pubmed
Zhu,
Effects of intra- and extracellular acidifications on single channel Kir2.3 currents.
1999,
Pubmed
,
Xenbase
Zhu,
Identification of endogenous outward currents in the human embryonic kidney (HEK 293) cell line.
1998,
Pubmed
