Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/34624
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dc.contributor.authorCapes, Deborah L. [UNIFESP]
dc.contributor.authorArcisio-Miranda, Manoel [UNIFESP]
dc.contributor.authorJarecki, Brian W.
dc.contributor.authorFrench, Robert J.
dc.contributor.authorChanda, Baron
dc.date.accessioned2016-01-24T14:17:55Z-
dc.date.available2016-01-24T14:17:55Z-
dc.date.issued2012-02-14
dc.identifierhttp://dx.doi.org/10.1073/pnas.1115575109
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America. Washington: Natl Acad Sciences, v. 109, n. 7, p. 2648-2653, 2012.
dc.identifier.issn0027-8424
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34624-
dc.description.abstractVoltage-dependent ion channels are crucial for generation and propagation of electrical activity in biological systems. the primary mechanism for voltage transduction in these proteins involves the movement of a voltage-sensing domain (D), which opens a gate located on the cytoplasmic side. A distinct conformational change in the selectivity filter near the extracellular side has been implicated in slow inactivation gating, which is important for spike frequency adaptation in neural circuits. However, it remains an open question whether gating transitions in the selectivity filter region are also actuated by voltage sensors. Here, we examine conformational coupling between each of the four voltage sensors and the outer pore of a eukaryotic voltage-dependent sodium channel. the voltage sensors of these sodium channels are not structurally symmetric and exhibit functional specialization. To track the conformational rearrangements of individual voltage-sensing domains, we recorded domain-specific gating pore currents. Our data show that, of the four voltage sensors, only the domain IV voltage sensor is coupled to the conformation of the selectivity filter region of the sodium channel. Trapping the outer pore in a particular conformation with a high-affinity toxin or disulphide crossbridge impedes the return of this voltage sensor to its resting conformation. Our findings directly establish that, in addition to the canonical electromechanical coupling between voltage sensor and inner pore gates of a sodium channel, gating transitions in the selectivity filter region are also coupled to the movement of a voltage sensor. Furthermore, our results also imply that the voltage sensor of domain IV is unique in this linkage and in the ability to initiate slow inactivation in sodium channels.en
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipShaw Scientist Award
dc.format.extent2648-2653
dc.language.isoeng
dc.publisherNatl Acad Sciences
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.rightsAcesso aberto
dc.subjectelectrophysiologyen
dc.subjectNav1.4en
dc.subjectouter pore conformationen
dc.titleGating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensoren
dc.typeArtigo
dc.contributor.institutionUniv Wisconsin
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Calgary
dc.description.affiliationUniv Wisconsin, Dept Neurosci, Madison, WI 53706 USA
dc.description.affiliationUniversidade Federal de São Paulo, Mol & Cellular Pharmacol Grad Program, BR-04023060 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, BR-04023060 São Paulo, Brazil
dc.description.affiliationUniv Calgary, Dept Physiol & Pharmacol, Calgary, AB T2N 4N1, Canada
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Mol & Cellular Pharmacol Grad Program, BR-04023060 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, BR-04023060 São Paulo, Brazil
dc.description.sponsorshipIDNational Institutes of Health: R01-GM084140
dc.identifier.doi10.1073/pnas.1115575109
dc.description.sourceWeb of Science
dc.identifier.wosWOS:000300489200094
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