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Biophys J
2007 Dec 15;9312:4159-72. doi: 10.1529/biophysj.107.107987.
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An inactivation gate in the selectivity filter of KCNQ1 potassium channels.
Gibor G
,
Yakubovich D
,
Rosenhouse-Dantsker A
,
Peretz A
,
Schottelndreier H
,
Seebohm G
,
Dascal N
,
Logothetis DE
,
Paas Y
,
Attali B
.
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Inactivation is an inherent property of most voltage-gated K(+) channels. While fast N-type inactivation has been analyzed in biophysical and structural details, the mechanisms underlying slow inactivation are yet poorly understood. Here, we characterized a slow inactivation mechanism in various KCNQ1 pore mutants, including L273F, which hinders entry of external Ba(2+) to its deep site in the pore and traps it by slowing its egress. Kinetic studies, molecular modeling, and dynamics simulations suggest that this slow inactivation involves conformational changes that converge to the outer carbonyl ring of the selectivity filter, where the backbone becomes less flexible. This mechanism involves acceleration of inactivation kinetics and enhancement of Ba(2+) trapping at elevated external K(+) concentrations. Hence, KCNQ1 slow inactivation considerably differs from C-type inactivation where vacation of K(+) from the filter was invoked. We suggest that trapping of K(+) at s(1) due to filter rigidity and hindrance of the dehydration-resolvation transition underlie the slow inactivation of KCNQ1 pore mutants.
Abitbol,
Stilbenes and fenamates rescue the loss of I(KS) channel function induced by an LQT5 mutation and other IsK mutants.
1999, Pubmed,
Xenbase
Abitbol,
Stilbenes and fenamates rescue the loss of I(KS) channel function induced by an LQT5 mutation and other IsK mutants.
1999,
Pubmed
,
Xenbase
Alagem,
The pore helix is involved in stabilizing the open state of inwardly rectifying K+ channels.
2003,
Pubmed
,
Xenbase
Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996,
Pubmed
,
Xenbase
Bernèche,
A gate in the selectivity filter of potassium channels.
2005,
Pubmed
Blunck,
How powerful is the dwell-time analysis of multichannel records?
1998,
Pubmed
Bähring,
Kinetic analysis of open- and closed-state inactivation transitions in human Kv4.2 A-type potassium channels.
2001,
Pubmed
Chapman,
Activation-dependent subconductance levels in the drk1 K channel suggest a subunit basis for ion permeation and gating.
1997,
Pubmed
,
Xenbase
Choi,
Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels.
1991,
Pubmed
Consiglio,
Influence of pore residues on permeation properties in the Kv2.1 potassium channel. Evidence for a selective functional interaction of K+ with the outer vestibule.
2003,
Pubmed
Cordero-Morales,
Voltage-dependent gating at the KcsA selectivity filter.
2006,
Pubmed
Cordero-Morales,
Molecular determinants of gating at the potassium-channel selectivity filter.
2006,
Pubmed
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Gibor,
External barium affects the gating of KCNQ1 potassium channels and produces a pore block via two discrete sites.
2004,
Pubmed
,
Xenbase
Harris,
A permanent ion binding site located between two gates of the Shaker K+ channel.
1998,
Pubmed
,
Xenbase
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Immke,
Potassium-dependent changes in the conformation of the Kv2.1 potassium channel pore.
1999,
Pubmed
Jentsch,
Neuronal KCNQ potassium channels: physiology and role in disease.
2000,
Pubmed
Jerng,
Inactivation gating of Kv4 potassium channels: molecular interactions involving the inner vestibule of the pore.
1999,
Pubmed
,
Xenbase
Jerng,
K+ channel inactivation mediated by the concerted action of the cytoplasmic N- and C-terminal domains.
1997,
Pubmed
,
Xenbase
Jiang,
The barium site in a potassium channel by x-ray crystallography.
2000,
Pubmed
Kiss,
Contribution of the selectivity filter to inactivation in potassium channels.
1999,
Pubmed
Klemic,
U-type inactivation of Kv3.1 and Shaker potassium channels.
2001,
Pubmed
,
Xenbase
Kurata,
A structural interpretation of voltage-gated potassium channel inactivation.
2006,
Pubmed
Kurata,
Altered state dependence of c-type inactivation in the long and short forms of human Kv1.5.
2001,
Pubmed
Larsson,
A conserved glutamate is important for slow inactivation in K+ channels.
2000,
Pubmed
,
Xenbase
Lenaeus,
Structural basis of TEA blockade in a model potassium channel.
2005,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
Loots,
Molecular coupling of S4 to a K(+) channel's slow inactivation gate.
2000,
Pubmed
Lu,
Probing ion permeation and gating in a K+ channel with backbone mutations in the selectivity filter.
2001,
Pubmed
,
Xenbase
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
MacKinnon,
Potassium channels and the atomic basis of selective ion conduction (Nobel Lecture).
2004,
Pubmed
Morais-Cabral,
Energetic optimization of ion conduction rate by the K+ selectivity filter.
2001,
Pubmed
Nerbonne,
Molecular physiology of cardiac repolarization.
2005,
Pubmed
Notredame,
T-Coffee: A novel method for fast and accurate multiple sequence alignment.
2000,
Pubmed
Olcese,
A conducting state with properties of a slow inactivated state in a shaker K(+) channel mutant.
2001,
Pubmed
,
Xenbase
Ortega-Sáenz,
Collapse of conductance is prevented by a glutamate residue conserved in voltage-dependent K(+) channels.
2000,
Pubmed
Paas,
Pore conformations and gating mechanism of a Cys-loop receptor.
2005,
Pubmed
,
Xenbase
Peretz,
Modulation of homomeric and heteromeric KCNQ1 channels by external acidification.
2002,
Pubmed
,
Xenbase
Proks,
The ligand-sensitive gate of a potassium channel lies close to the selectivity filter.
2003,
Pubmed
,
Xenbase
Pusch,
Activation and inactivation of homomeric KvLQT1 potassium channels.
1998,
Pubmed
,
Xenbase
Pusch,
Increase of the single-channel conductance of KvLQT1 potassium channels induced by the association with minK.
1998,
Pubmed
,
Xenbase
Pusch,
Gating and flickery block differentially affected by rubidium in homomeric KCNQ1 and heteromeric KCNQ1/KCNE1 potassium channels.
2000,
Pubmed
,
Xenbase
Roden,
Long QT syndrome: reduced repolarization reserve and the genetic link.
2006,
Pubmed
Sanguinetti,
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
1996,
Pubmed
,
Xenbase
Schwede,
SWISS-MODEL: An automated protein homology-modeling server.
2003,
Pubmed
Seebohm,
Tight coupling of rubidium conductance and inactivation in human KCNQ1 potassium channels.
2003,
Pubmed
,
Xenbase
Seebohm,
Mutation of colocalized residues of the pore helix and transmembrane segments S5 and S6 disrupt deactivation and modify inactivation of KCNQ1 K+ channels.
2005,
Pubmed
,
Xenbase
Seebohm,
Identification of specific pore residues mediating KCNQ1 inactivation. A novel mechanism for long QT syndrome.
2001,
Pubmed
,
Xenbase
Sesti,
Single-channel characteristics of wild-type IKs channels and channels formed with two minK mutants that cause long QT syndrome.
1998,
Pubmed
,
Xenbase
Shalaby,
Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome.
1997,
Pubmed
,
Xenbase
Shamgar,
Calmodulin is essential for cardiac IKS channel gating and assembly: impaired function in long-QT mutations.
2006,
Pubmed
Starkus,
Ion conduction through C-type inactivated Shaker channels.
1997,
Pubmed
,
Xenbase
Swartz,
Towards a structural view of gating in potassium channels.
2004,
Pubmed
Tristani-Firouzi,
Voltage-dependent inactivation of the human K+ channel KvLQT1 is eliminated by association with minimal K+ channel (minK) subunits.
1998,
Pubmed
,
Xenbase
Woodhull,
Ionic blockage of sodium channels in nerve.
1973,
Pubmed
Yang,
Single-channel properties of IKs potassium channels.
1998,
Pubmed
,
Xenbase
Yellen,
The moving parts of voltage-gated ion channels.
1998,
Pubmed
Zagotta,
Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB.
1990,
Pubmed
,
Xenbase
Zhou,
Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors.
2001,
Pubmed
,
Xenbase
Zhou,
Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution.
2001,
Pubmed
Zhou,
The occupancy of ions in the K+ selectivity filter: charge balance and coupling of ion binding to a protein conformational change underlie high conduction rates.
2003,
Pubmed
Zhou,
Ion binding affinity in the cavity of the KcsA potassium channel.
2004,
Pubmed
