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Coupling Interactions between Voltage Sensors of the Sodium Channel as Revealed by Site-specific Measurements
The voltage-sensing S4 segments in the sodium channel undergo conformational rearrangements in response to changes in the electric field. However, it remains unclear whether these structures move independently or in a coordinated manner. Previously, site-directed fluorescence measurements were shown...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217449/ https://www.ncbi.nlm.nih.gov/pubmed/14981134 http://dx.doi.org/10.1085/jgp.200308971 |
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author | Chanda, Baron Asamoah, Osei Kwame Bezanilla, Francisco |
author_facet | Chanda, Baron Asamoah, Osei Kwame Bezanilla, Francisco |
author_sort | Chanda, Baron |
collection | PubMed |
description | The voltage-sensing S4 segments in the sodium channel undergo conformational rearrangements in response to changes in the electric field. However, it remains unclear whether these structures move independently or in a coordinated manner. Previously, site-directed fluorescence measurements were shown to track S4 transitions in each of the four domains (Chanda, B., and F. Bezanilla. 2002. J. Gen. Physiol. 120:629–645). Here, using a similar technique, we provide direct evidence of coupling interactions between voltage sensors in the sodium channel. Pairwise interactions between S4s were evaluated by comparing site-specific conformational changes in the presence and absence of a gating perturbation in a distal domain. Reciprocity of effect, a fundamental property of thermodynamically coupled systems, was measured by generating converse mutants. The magnitude of a local gating perturbation induced by a remote S4 mutation depends on the coupling strength and the relative equilibrium positions of the two voltage sensors. In general, our data indicates that the movement of all four voltage sensors in the sodium channel are coupled to a varying extent. Moreover, a gating perturbation in S4-DI has the largest effect on the activation of S4-DIV and vice versa, demonstrating an energetic linkage between S4-DI and S4-DIV. This result suggests a physical mechanism by which the activation and inactivation process may be coupled in voltage-gated sodium channels. In addition, we propose that cooperative interactions between voltage sensors may be the mechanistic basis for the fast activation kinetics of the sodium channel. |
format | Text |
id | pubmed-2217449 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22174492008-03-21 Coupling Interactions between Voltage Sensors of the Sodium Channel as Revealed by Site-specific Measurements Chanda, Baron Asamoah, Osei Kwame Bezanilla, Francisco J Gen Physiol Article The voltage-sensing S4 segments in the sodium channel undergo conformational rearrangements in response to changes in the electric field. However, it remains unclear whether these structures move independently or in a coordinated manner. Previously, site-directed fluorescence measurements were shown to track S4 transitions in each of the four domains (Chanda, B., and F. Bezanilla. 2002. J. Gen. Physiol. 120:629–645). Here, using a similar technique, we provide direct evidence of coupling interactions between voltage sensors in the sodium channel. Pairwise interactions between S4s were evaluated by comparing site-specific conformational changes in the presence and absence of a gating perturbation in a distal domain. Reciprocity of effect, a fundamental property of thermodynamically coupled systems, was measured by generating converse mutants. The magnitude of a local gating perturbation induced by a remote S4 mutation depends on the coupling strength and the relative equilibrium positions of the two voltage sensors. In general, our data indicates that the movement of all four voltage sensors in the sodium channel are coupled to a varying extent. Moreover, a gating perturbation in S4-DI has the largest effect on the activation of S4-DIV and vice versa, demonstrating an energetic linkage between S4-DI and S4-DIV. This result suggests a physical mechanism by which the activation and inactivation process may be coupled in voltage-gated sodium channels. In addition, we propose that cooperative interactions between voltage sensors may be the mechanistic basis for the fast activation kinetics of the sodium channel. The Rockefeller University Press 2004-03 /pmc/articles/PMC2217449/ /pubmed/14981134 http://dx.doi.org/10.1085/jgp.200308971 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Chanda, Baron Asamoah, Osei Kwame Bezanilla, Francisco Coupling Interactions between Voltage Sensors of the Sodium Channel as Revealed by Site-specific Measurements |
title | Coupling Interactions between Voltage Sensors of the Sodium Channel as Revealed by Site-specific Measurements |
title_full | Coupling Interactions between Voltage Sensors of the Sodium Channel as Revealed by Site-specific Measurements |
title_fullStr | Coupling Interactions between Voltage Sensors of the Sodium Channel as Revealed by Site-specific Measurements |
title_full_unstemmed | Coupling Interactions between Voltage Sensors of the Sodium Channel as Revealed by Site-specific Measurements |
title_short | Coupling Interactions between Voltage Sensors of the Sodium Channel as Revealed by Site-specific Measurements |
title_sort | coupling interactions between voltage sensors of the sodium channel as revealed by site-specific measurements |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2217449/ https://www.ncbi.nlm.nih.gov/pubmed/14981134 http://dx.doi.org/10.1085/jgp.200308971 |
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