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Proc Natl Acad Sci U S A
2005 Dec 20;10251:18718-23. doi: 10.1073/pnas.0505766102.
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Optical detection of rate-determining ion-modulated conformational changes of the ether-à-go-go K+ channel voltage sensor.
Bannister JP
,
Chanda B
,
Bezanilla F
,
Papazian DM
.
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In voltage-dependent ether-à-go-go (eag) K+ channels, the process of activation is modulated by Mg2+ and other divalent cations, which bind to a site in the voltage sensor and slow channel opening. Previous analysis of eag ionic and gating currents indicated that Mg2+ has a much larger effect on ionic than gating current kinetics. From this, we hypothesized that ion binding modulates voltage sensor conformational changes that are poorly represented in gating current recordings. We have now tested this proposal by using a combined electrophysiological and optical approach. We find that a fluorescent probe attached near S4 in the voltage sensor reports on two phases of the activation process. One component of the optical signal corresponds to the main charge-moving conformational changes of the voltage sensor. This is the phase of activation that is well represented in gating current recordings. Another component of the optical signal reflects voltage sensor conformational changes that occur at more hyperpolarized potentials. These transitions, which are rate-determining for activation and highly modulated by Mg2+, have not been detected in gating current recordings. Our results demonstrate that the eag voltage sensor undergoes conformational changes that have gone undetected in electrical measurements. These transitions account for the time course of eag activation in the presence and absence of extracellular Mg2+.
Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996, Pubmed,
Xenbase
Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996,
Pubmed
,
Xenbase
Bezanilla,
Inactivation of the sodium channel. I. Sodium current experiments.
1977,
Pubmed
Bezanilla,
The voltage sensor in voltage-dependent ion channels.
2000,
Pubmed
Bezanilla,
Gating of Shaker K+ channels: II. The components of gating currents and a model of channel activation.
1994,
Pubmed
,
Xenbase
Cha,
Characterizing voltage-dependent conformational changes in the Shaker K+ channel with fluorescence.
1997,
Pubmed
,
Xenbase
Cha,
Structural implications of fluorescence quenching in the Shaker K+ channel.
1998,
Pubmed
Chanda,
Coupling interactions between voltage sensors of the sodium channel as revealed by site-specific measurements.
2004,
Pubmed
COLE,
Potassium ion current in the squid giant axon: dynamic characteristic.
1960,
Pubmed
Curran,
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
1995,
Pubmed
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Jiang,
X-ray structure of a voltage-dependent K+ channel.
2003,
Pubmed
Kozak,
At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells.
1987,
Pubmed
MacKinnon,
Determination of the subunit stoichiometry of a voltage-activated potassium channel.
1991,
Pubmed
,
Xenbase
Mannuzzu,
Direct physical measure of conformational rearrangement underlying potassium channel gating.
1996,
Pubmed
,
Xenbase
Papazian,
Alteration of voltage-dependence of Shaker potassium channel by mutations in the S4 sequence.
1991,
Pubmed
,
Xenbase
Saganich,
Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain.
2001,
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,
Individual subunits contribute independently to slow gating of bovine EAG potassium channels.
1999,
Pubmed
Schoppa,
Activation of Shaker potassium channels. III. An activation gating model for wild-type and V2 mutant channels.
1998,
Pubmed
,
Xenbase
Seoh,
Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel.
1996,
Pubmed
,
Xenbase
Silverman,
Binding site in eag voltage sensor accommodates a variety of ions and is accessible in closed channel.
2004,
Pubmed
,
Xenbase
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,
Structural basis of two-stage voltage-dependent activation in K+ channels.
2003,
Pubmed
,
Xenbase
Smith,
Fast and slow voltage sensor movements in HERG potassium channels.
2002,
Pubmed
,
Xenbase
Stefani,
Gating of Shaker K+ channels: I. Ionic and gating currents.
1994,
Pubmed
,
Xenbase
Tang,
Extracellular Mg(2+) modulates slow gating transitions and the opening of Drosophila ether-à-Go-Go potassium channels.
2000,
Pubmed
,
Xenbase
Taylor,
Sodium and gating current time shifts resulting from changes in initial conditions.
1983,
Pubmed
Tempel,
Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila.
1987,
Pubmed
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
Warmke,
A family of potassium channel genes related to eag in Drosophila and mammals.
1994,
Pubmed
Warmke,
A distinct potassium channel polypeptide encoded by the Drosophila eag locus.
1991,
Pubmed
Zagotta,
Shaker potassium channel gating. III: Evaluation of kinetic models for activation.
1994,
Pubmed
,
Xenbase
