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Channels (Austin)
2007 Jan 01;16:429-37. doi: 10.4161/chan.1.6.5760.
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Differences between ion binding to eag and HERG voltage sensors contribute to differential regulation of activation and deactivation gating.
Lin MC, Papazian DM.
???displayArticle.abstract??? HERG (KCNH2) and ether-à-go-go (eag) (KCNH1) are members of the same subfamily of voltage-gated K+ channels. In eag, voltage-dependent activation is significantly slowed by extracellular divalent cations. To exert this effect, ions bind to a site located between transmembrane segments S2 and S3 in the voltage sensor domain where they interact with acidic residues that are conserved only among members of the eag subfamily. In HERG channels, extracellular divalent ions significantly accelerate deactivation. To investigate the ionbinding site in HERG, acidic residues in S2 and S3 were neutralized singly or in pairs to alanine, and the functional effects of extracellular Mg(2+) were characterized in Xenopus oocytes. To modulate deactivation kinetics in HERG, divalent cations interact with eag subfamily-specific acidic residues (D460 and D509) and also with an acidic residue in S2 (D456) that is widely conserved in the voltage-gated channel superfamily. In contrast, the analogous widely-conserved residue does not contribute to the ion-binding site that modulates activation kinetics in eag. We propose that structural differences between the ion-binding sites in the eag and HERG voltage sensors contribute to the differential regulation of activation and deactivation gating in these channels. A previously proposed model for S4 conformational changes during voltagedependent activation can account for the differential regulation of gating seen in eag and HERG.
Abbott,
MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia.
1999, Pubmed,
Xenbase
Abbott,
MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia.
1999,
Pubmed
,
Xenbase Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996,
Pubmed
,
Xenbase Andersson,
Structural basis for the negative allostery between Ca(2+)- and Mg(2+)-binding in the intracellular Ca(2+)-receptor calbindin D9k.
1997,
Pubmed Bannister,
Optical detection of rate-determining ion-modulated conformational changes of the ether-à-go-go K+ channel voltage sensor.
2005,
Pubmed
,
Xenbase Bezanilla,
Inactivation of the sodium channel. I. Sodium current experiments.
1977,
Pubmed Bezanilla,
Molecular basis of gating charge immobilization in Shaker potassium channels.
1991,
Pubmed
,
Xenbase Courcot,
Crystal and electronic structures of magnesium(II), copper(II), and mixed magnesium(II)-copper(II) complexes of the quinoline half of styrylquinoline-type HIV-1 integrase inhibitors.
2007,
Pubmed Curran,
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
1995,
Pubmed Dumaine,
Molecular mechanisms underlying the long QT syndrome.
2002,
Pubmed Elinder,
Metal ion effects on ion channel gating.
2003,
Pubmed Fernandez,
Molecular mapping of a site for Cd2+-induced modification of human ether-à-go-go-related gene (hERG) channel activation.
2005,
Pubmed
,
Xenbase Ganetzky,
The eag family of K+ channels in Drosophila and mammals.
1999,
Pubmed Goldgur,
Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: a platform for antiviral drug design.
1999,
Pubmed Hancox,
Time course and voltage dependence of expressed HERG current compared with native "rapid" delayed rectifier K current during the cardiac ventricular action potential.
1998,
Pubmed Janeira,
Torsades de pointes and long QT syndromes.
1995,
Pubmed Jogini,
Dynamics of the Kv1.2 voltage-gated K+ channel in a membrane environment.
2007,
Pubmed Johnson,
Human ether-à-go-go-related gene K+ channel gating probed with extracellular ca2+. Evidence for two distinct voltage sensors.
1999,
Pubmed Johnson,
A novel extracellular calcium sensing mechanism in voltage-gated potassium ion channels.
2001,
Pubmed Jones,
Cardiac IKr channels minimally comprise hERG 1a and 1b subunits.
2004,
Pubmed Landt,
A general method for rapid site-directed mutagenesis using the polymerase chain reaction.
1990,
Pubmed Larsen,
Ligand-induced domain movement in pyruvate kinase: structure of the enzyme from rabbit muscle with Mg2+, K+, and L-phospholactate at 2.7 A resolution.
1997,
Pubmed Liu,
Negative charges in the transmembrane domains of the HERG K channel are involved in the activation- and deactivation-gating processes.
2003,
Pubmed
,
Xenbase London,
Two isoforms of the mouse ether-a-go-go-related gene coassemble to form channels with properties similar to the rapidly activating component of the cardiac delayed rectifier K+ current.
1997,
Pubmed
,
Xenbase Long,
Voltage sensor of Kv1.2: structural basis of electromechanical coupling.
2005,
Pubmed Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed Paavonen,
Functional characterization of the common amino acid 897 polymorphism of the cardiac potassium channel KCNH2 (HERG).
2003,
Pubmed Papazian,
Alteration of voltage-dependence of Shaker potassium channel by mutations in the S4 sequence.
1991,
Pubmed
,
Xenbase Po,
Modulation of HERG potassium channels by extracellular magnesium and quinidine.
1999,
Pubmed
,
Xenbase Sanchez-Chapula,
Altered gating of HERG potassium channels by cobalt and lanthanum.
2000,
Pubmed
,
Xenbase Sanguinetti,
hERG potassium channels and cardiac arrhythmia.
2006,
Pubmed Sanguinetti,
Predicting drug-hERG channel interactions that cause acquired long QT syndrome.
2005,
Pubmed Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase Schönherr,
Conformational switch between slow and fast gating modes: allosteric regulation of voltage sensor mobility in the EAG K+ channel.
2002,
Pubmed
,
Xenbase Schönherr,
Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel.
1996,
Pubmed
,
Xenbase Schoppa,
The size of gating charge in wild-type and mutant Shaker potassium channels.
1992,
Pubmed Seoh,
Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel.
1996,
Pubmed
,
Xenbase Sesti,
A common polymorphism associated with antibiotic-induced cardiac arrhythmia.
2000,
Pubmed Silverman,
Mg(2+) modulates voltage-dependent activation in ether-à-go-go potassium channels by binding between transmembrane segments S2 and S3.
2000,
Pubmed
,
Xenbase Silverman,
Binding site in eag voltage sensor accommodates a variety of ions and is accessible in closed channel.
2004,
Pubmed
,
Xenbase Silverman,
Structural basis of two-stage voltage-dependent activation in K+ channels.
2003,
Pubmed
,
Xenbase Smith,
The inward rectification mechanism of the HERG cardiac potassium channel.
1996,
Pubmed Spector,
Fast inactivation causes rectification of the IKr channel.
1996,
Pubmed
,
Xenbase Tang,
Extracellular Mg(2+) modulates slow gating transitions and the opening of Drosophila ether-à-Go-Go potassium channels.
2000,
Pubmed
,
Xenbase Terlau,
Extracellular Mg2+ regulates activation of rat eag potassium channel.
1996,
Pubmed
,
Xenbase Timpe,
Expression of functional potassium channels from Shaker cDNA in Xenopus oocytes.
1988,
Pubmed
,
Xenbase Tiwari-Woodruff,
Voltage-dependent structural interactions in the Shaker K(+) channel.
2000,
Pubmed
,
Xenbase Tseng,
I(Kr): the hERG channel.
2001,
Pubmed Viloria,
Differential effects of amino-terminal distal and proximal domains in the regulation of human erg K(+) channel gating.
2000,
Pubmed
,
Xenbase Walker,
Congenital and acquired long QT syndromes.
2003,
Pubmed Wang,
Time, voltage and ionic concentration dependence of rectification of h-erg expressed in Xenopus oocytes.
1996,
Pubmed
,
Xenbase Warmke,
A family of potassium channel genes related to eag in Drosophila and mammals.
1994,
Pubmed
