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Concerted gating mechanism underlying KATP channel inhibition by ATP.
Drain P
,
Geng X
,
Li L
.
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KATP channels assemble from four regulatory SUR1 and four pore-forming Kir6.2 subunits. At the single-channel current level, ATP-dependent gating transitions between the active burst and the inactive interburst conformations underlie inhibition of the KATP channel by intracellular ATP. Previously, we identified a slow gating mutation, T171A in the Kir6.2 subunit, which dramatically reduces rates of burst to interburst transitions in Kir6.2DeltaC26 channels without SUR1 in the absence of ATP. Here, we constructed all possible mutations at position 171 in Kir6.2DeltaC26 channels without SUR1. Only four substitutions, 171A, 171F, 171H, and 171S, gave rise to functional channels, each increasing Ki,ATP for ATP inhibition by >55-fold and slowing gating to the interburst by >35-fold. Moreover, we investigated the role of individual Kir6.2 subunits in the gating by comparing burst to interburst transition rates of channels constructed from different combinations of slow 171A and fast T171 "wild-type" subunits. The relationship between gating transition rate and number of slow subunits is exponential, which excludes independent gating models where any one subunit is sufficient for inhibition gating. Rather, our results support mechanisms where four ATP sites independently can control a single gate formed by the concerted action of all four Kir6.2 subunit inner helices of the KATP channel.
Aguilar-Bryan,
Of mice and men: K(ATP) channels and insulin secretion.
2001, Pubmed
Aguilar-Bryan,
Of mice and men: K(ATP) channels and insulin secretion.
2001,
Pubmed
Aguilar-Bryan,
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
1995,
Pubmed
Alagem,
The pore helix is involved in stabilizing the open state of inwardly rectifying K+ channels.
2003,
Pubmed
,
Xenbase
Alekseev,
Ligand-insensitive state of cardiac ATP-sensitive K+ channels. Basis for channel opening.
1998,
Pubmed
Amoroso,
Glucose, sulfonylureas, and neurotransmitter release: role of ATP-sensitive K+ channels.
1990,
Pubmed
Armstrong,
Time course of TEA(+)-induced anomalous rectification in squid giant axons.
1966,
Pubmed
Armstrong,
Ionic pores, gates, and gating currents.
1974,
Pubmed
Ashcroft,
Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells.
,
Pubmed
Ashcroft,
Adenosine 5'-triphosphate-sensitive potassium channels.
1988,
Pubmed
Babenko,
Pharmaco-topology of sulfonylurea receptors. Separate domains of the regulatory subunits of K(ATP) channel isoforms are required for selective interaction with K(+) channel openers.
2000,
Pubmed
Babenko,
The N-terminus of KIR6.2 limits spontaneous bursting and modulates the ATP-inhibition of KATP channels.
1999,
Pubmed
Babenko,
Two regions of sulfonylurea receptor specify the spontaneous bursting and ATP inhibition of KATP channel isoforms.
1999,
Pubmed
Babenko,
The tolbutamide site of SUR1 and a mechanism for its functional coupling to K(ATP) channel closure.
1999,
Pubmed
Capener,
Homology modeling and molecular dynamics simulation studies of an inward rectifier potassium channel.
2000,
Pubmed
Clement,
Association and stoichiometry of K(ATP) channel subunits.
1997,
Pubmed
Cook,
Intracellular ATP directly blocks K+ channels in pancreatic B-cells.
,
Pubmed
Deutsch,
Surface charge and properties of cardiac ATP-sensitive K+ channels.
1994,
Pubmed
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Drain,
Regulation of Shaker K+ channel inactivation gating by the cAMP-dependent protein kinase.
1994,
Pubmed
,
Xenbase
Drain,
KATP channel inhibition by ATP requires distinct functional domains of the cytoplasmic C terminus of the pore-forming subunit.
1998,
Pubmed
,
Xenbase
Fan,
Phosphoinositides decrease ATP sensitivity of the cardiac ATP-sensitive K(+) channel. A molecular probe for the mechanism of ATP-sensitive inhibition.
1999,
Pubmed
Gillis,
Effects of sulfonamides on a metabolite-regulated ATPi-sensitive K+ channel in rat pancreatic B-cells.
1989,
Pubmed
Gribble,
The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide.
1997,
Pubmed
,
Xenbase
Guo,
Mechanism of rectification in inward-rectifier K+ channels.
2003,
Pubmed
,
Xenbase
Hackos,
Scanning the intracellular S6 activation gate in the shaker K+ channel.
2002,
Pubmed
,
Xenbase
Holmgren,
The activation gate of a voltage-gated K+ channel can be trapped in the open state by an intersubunit metal bridge.
1998,
Pubmed
Holmgren,
Trapping of organic blockers by closing of voltage-dependent K+ channels: evidence for a trap door mechanism of activation gating.
1997,
Pubmed
Inagaki,
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
1995,
Pubmed
Inagaki,
Subunit stoichiometry of the pancreatic beta-cell ATP-sensitive K+ channel.
1997,
Pubmed
Jiang,
Crystal structure and mechanism of a calcium-gated potassium channel.
2002,
Pubmed
Jiang,
The open pore conformation of potassium channels.
2002,
Pubmed
John,
The sulphonylurea receptor SUR1 regulates ATP-sensitive mouse Kir6.2 K+ channels linked to the green fluorescent protein in human embryonic kidney cells (HEK 293).
1998,
Pubmed
Jones,
Multiple sites of interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2.
2001,
Pubmed
Koster,
ATP inhibition of KATP channels: control of nucleotide sensitivity by the N-terminal domain of the Kir6.2 subunit.
1999,
Pubmed
Kuo,
Crystal structure of the potassium channel KirBac1.1 in the closed state.
2003,
Pubmed
Ledwell,
Mutations in the S4 region isolate the final voltage-dependent cooperative step in potassium channel activation.
1999,
Pubmed
,
Xenbase
Lee,
The high-affinity sulphonylurea receptor regulates KATP channels in nerve terminals of the rat motor cortex.
1996,
Pubmed
Li,
The I182 region of k(ir)6.2 is closely associated with ligand binding in K(ATP) channel inhibition by ATP.
2000,
Pubmed
,
Xenbase
Li,
Open state destabilization by ATP occupancy is mechanism speeding burst exit underlying KATP channel inhibition by ATP.
2002,
Pubmed
,
Xenbase
Liu,
Gated access to the pore of a voltage-dependent K+ channel.
1997,
Pubmed
Loussouarn,
Structure and dynamics of the pore of inwardly rectifying K(ATP) channels.
2000,
Pubmed
Loussouarn,
Flexibility of the Kir6.2 inward rectifier K(+) channel pore.
2001,
Pubmed
Lu,
Coupling between voltage sensors and activation gate in voltage-gated K+ channels.
2002,
Pubmed
,
Xenbase
Ma,
Role of ER export signals in controlling surface potassium channel numbers.
2001,
Pubmed
,
Xenbase
MacGregor,
Nucleotides and phospholipids compete for binding to the C terminus of KATP channels.
2002,
Pubmed
Markworth,
ATP4- mediates closure of pancreatic beta-cell ATP-sensitive potassium channels by interaction with 1 of 4 identical sites.
2000,
Pubmed
McIntosh,
Mutagenesis of segment 487Phe-Ser-Arg-Asp-Arg-Lys492 of sarcoplasmic reticulum Ca2+-ATPase produces pumps defective in ATP binding.
1996,
Pubmed
Miki,
ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis.
2001,
Pubmed
Nichols,
ATP dependence of KATP channel kinetics in isolated membrane patches from rat ventricle.
1991,
Pubmed
Nichols,
Adenosine diphosphate as an intracellular regulator of insulin secretion.
1996,
Pubmed
Nishida,
Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution.
2002,
Pubmed
Noma,
ATP-regulated K+ channels in cardiac muscle.
,
Pubmed
Phillips,
Gating dependence of inner pore access in inward rectifier K(+) channels.
2003,
Pubmed
Proks,
Involvement of the N-terminus of Kir6.2 in the inhibition of the KATP channel by ATP.
1999,
Pubmed
,
Xenbase
Proks,
Mutations within the P-loop of Kir6.2 modulate the intraburst kinetics of the ATP-sensitive potassium channel.
2001,
Pubmed
,
Xenbase
Proks,
The ligand-sensitive gate of a potassium channel lies close to the selectivity filter.
2003,
Pubmed
,
Xenbase
Qin,
Kinetics of ATP-sensitive K+ channel revealed with oil-gate concentration jump method.
1989,
Pubmed
Reidhaar-Olson,
Random mutagenesis of protein sequences using oligonucleotide cassettes.
1991,
Pubmed
Reimann,
Involvement of the n-terminus of Kir6.2 in coupling to the sulphonylurea receptor.
1999,
Pubmed
,
Xenbase
Ribalet,
Molecular basis for Kir6.2 channel inhibition by adenine nucleotides.
2003,
Pubmed
Schmid-Antomarchi,
K+ channel openers activate brain sulfonylurea-sensitive K+ channels and block neurosecretion.
1990,
Pubmed
Schoppa,
Activation of Shaker potassium channels. II. Kinetics of the V2 mutant channel.
1998,
Pubmed
,
Xenbase
Schoppa,
Activation of Shaker potassium channels. III. An activation gating model for wild-type and V2 mutant channels.
1998,
Pubmed
,
Xenbase
Sharma,
The C terminus of SUR1 is required for trafficking of KATP channels.
1999,
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,
Control of rectification and gating of cloned KATP channels by the Kir6.2 subunit.
1997,
Pubmed
Shyng,
Octameric stoichiometry of the KATP channel complex.
1997,
Pubmed
Sigworth,
Data transformations for improved display and fitting of single-channel dwell time histograms.
1987,
Pubmed
Takano,
Cytoplasmic terminus domains of Kir6.x confer different nucleotide-dependent gating on the ATP-sensitive K+ channel.
1998,
Pubmed
Tanabe,
Direct photoaffinity labeling of Kir6.2 by [gamma-(32)P]ATP-[gamma]4-azidoanilide.
2000,
Pubmed
,
Xenbase
Tanabe,
Direct photoaffinity labeling of the Kir6.2 subunit of the ATP-sensitive K+ channel by 8-azido-ATP.
1999,
Pubmed
,
Xenbase
Terzic,
Dualistic behavior of ATP-sensitive K+ channels toward intracellular nucleoside diphosphates.
1994,
Pubmed
Trapp,
Molecular analysis of ATP-sensitive K channel gating and implications for channel inhibition by ATP.
1998,
Pubmed
,
Xenbase
Trapp,
Identification of residues contributing to the ATP binding site of Kir6.2.
2003,
Pubmed
,
Xenbase
Trube,
Inward-rectifying channels in isolated patches of the heart cell membrane: ATP-dependence and comparison with cell-attached patches.
1984,
Pubmed
Tucker,
Mapping of the physical interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2.
1999,
Pubmed
Tucker,
Molecular determinants of KATP 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
Vanoye,
The carboxyl termini of K(ATP) channels bind nucleotides.
2002,
Pubmed
Xiao,
Localization of PIP2 activation gate in inward rectifier K+ channels.
2003,
Pubmed
,
Xenbase
Yellen,
The voltage-gated potassium channels and their relatives.
2002,
Pubmed
Zagotta,
Shaker potassium channel gating. II: Transitions in the activation pathway.
1994,
Pubmed
,
Xenbase
Zagotta,
Shaker potassium channel gating. III: Evaluation of kinetic models for activation.
1994,
Pubmed
,
Xenbase
Zerangue,
A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels.
1999,
Pubmed
,
Xenbase
del Camino,
Blocker protection in the pore of a voltage-gated K+ channel and its structural implications.
2000,
Pubmed
del Camino,
Tight steric closure at the intracellular activation gate of a voltage-gated K(+) channel.
2001,
Pubmed
