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β-Scorpion Toxin Modifies Gating Transitions in All Four Voltage Sensors of the Sodium Channel

Several naturally occurring polypeptide neurotoxins target specific sites on the voltage-gated sodium channels. Of these, the gating modifier toxins alter the behavior of the sodium channels by stabilizing transient intermediate states in the channel gating pathway. Here we have used an integrated a...

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Autores principales: Campos, Fabiana V., Chanda, Baron, Beirão, Paulo S.L., Bezanilla, Francisco
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151646/
https://www.ncbi.nlm.nih.gov/pubmed/17698594
http://dx.doi.org/10.1085/jgp.200609719
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author Campos, Fabiana V.
Chanda, Baron
Beirão, Paulo S.L.
Bezanilla, Francisco
author_facet Campos, Fabiana V.
Chanda, Baron
Beirão, Paulo S.L.
Bezanilla, Francisco
author_sort Campos, Fabiana V.
collection PubMed
description Several naturally occurring polypeptide neurotoxins target specific sites on the voltage-gated sodium channels. Of these, the gating modifier toxins alter the behavior of the sodium channels by stabilizing transient intermediate states in the channel gating pathway. Here we have used an integrated approach that combines electrophysiological and spectroscopic measurements to determine the structural rearrangements modified by the β-scorpion toxin Ts1. Our data indicate that toxin binding to the channel is restricted to a single binding site on domain II voltage sensor. Analysis of Cole-Moore shifts suggests that the number of closed states in the activation sequence prior to channel opening is reduced in the presence of toxin. Measurements of charge–voltage relationships show that a fraction of the gating charge is immobilized in Ts1-modified channels. Interestingly, the charge–voltage relationship also shows an additional component at hyperpolarized potentials. Site-specific fluorescence measurements indicate that in presence of the toxin the voltage sensor of domain II remains trapped in the activated state. Furthermore, the binding of the toxin potentiates the activation of the other three voltage sensors of the sodium channel to more hyperpolarized potentials. These findings reveal how the binding of β-scorpion toxin modifies channel function and provides insight into early gating transitions of sodium channels.
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spelling pubmed-21516462008-03-01 β-Scorpion Toxin Modifies Gating Transitions in All Four Voltage Sensors of the Sodium Channel Campos, Fabiana V. Chanda, Baron Beirão, Paulo S.L. Bezanilla, Francisco J Gen Physiol Articles Several naturally occurring polypeptide neurotoxins target specific sites on the voltage-gated sodium channels. Of these, the gating modifier toxins alter the behavior of the sodium channels by stabilizing transient intermediate states in the channel gating pathway. Here we have used an integrated approach that combines electrophysiological and spectroscopic measurements to determine the structural rearrangements modified by the β-scorpion toxin Ts1. Our data indicate that toxin binding to the channel is restricted to a single binding site on domain II voltage sensor. Analysis of Cole-Moore shifts suggests that the number of closed states in the activation sequence prior to channel opening is reduced in the presence of toxin. Measurements of charge–voltage relationships show that a fraction of the gating charge is immobilized in Ts1-modified channels. Interestingly, the charge–voltage relationship also shows an additional component at hyperpolarized potentials. Site-specific fluorescence measurements indicate that in presence of the toxin the voltage sensor of domain II remains trapped in the activated state. Furthermore, the binding of the toxin potentiates the activation of the other three voltage sensors of the sodium channel to more hyperpolarized potentials. These findings reveal how the binding of β-scorpion toxin modifies channel function and provides insight into early gating transitions of sodium channels. The Rockefeller University Press 2007-09 /pmc/articles/PMC2151646/ /pubmed/17698594 http://dx.doi.org/10.1085/jgp.200609719 Text en Copyright © 2007, 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 Articles
Campos, Fabiana V.
Chanda, Baron
Beirão, Paulo S.L.
Bezanilla, Francisco
β-Scorpion Toxin Modifies Gating Transitions in All Four Voltage Sensors of the Sodium Channel
title β-Scorpion Toxin Modifies Gating Transitions in All Four Voltage Sensors of the Sodium Channel
title_full β-Scorpion Toxin Modifies Gating Transitions in All Four Voltage Sensors of the Sodium Channel
title_fullStr β-Scorpion Toxin Modifies Gating Transitions in All Four Voltage Sensors of the Sodium Channel
title_full_unstemmed β-Scorpion Toxin Modifies Gating Transitions in All Four Voltage Sensors of the Sodium Channel
title_short β-Scorpion Toxin Modifies Gating Transitions in All Four Voltage Sensors of the Sodium Channel
title_sort β-scorpion toxin modifies gating transitions in all four voltage sensors of the sodium channel
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151646/
https://www.ncbi.nlm.nih.gov/pubmed/17698594
http://dx.doi.org/10.1085/jgp.200609719
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