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Molecular mechanism for depolarization-induced modulation of Kv channel closure

Voltage-dependent potassium (Kv) channels provide the repolarizing power that shapes the action potential duration and helps control the firing frequency of neurons. The K(+) permeation through the channel pore is controlled by an intracellularly located bundle-crossing (BC) gate that communicates w...

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Autores principales: Labro, Alain J., Lacroix, Jerome J., Villalba-Galea, Carlos A., Snyders, Dirk J., Bezanilla, Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483114/
https://www.ncbi.nlm.nih.gov/pubmed/23071266
http://dx.doi.org/10.1085/jgp.201210817
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author Labro, Alain J.
Lacroix, Jerome J.
Villalba-Galea, Carlos A.
Snyders, Dirk J.
Bezanilla, Francisco
author_facet Labro, Alain J.
Lacroix, Jerome J.
Villalba-Galea, Carlos A.
Snyders, Dirk J.
Bezanilla, Francisco
author_sort Labro, Alain J.
collection PubMed
description Voltage-dependent potassium (Kv) channels provide the repolarizing power that shapes the action potential duration and helps control the firing frequency of neurons. The K(+) permeation through the channel pore is controlled by an intracellularly located bundle-crossing (BC) gate that communicates with the voltage-sensing domains (VSDs). During prolonged membrane depolarizations, most Kv channels display C-type inactivation that halts K(+) conduction through constriction of the K(+) selectivity filter. Besides triggering C-type inactivation, we show that in Shaker and Kv1.2 channels (expressed in Xenopus laevis oocytes), prolonged membrane depolarizations also slow down the kinetics of VSD deactivation and BC gate closure during the subsequent membrane repolarization. Measurements of deactivating gating currents (reporting VSD movement) and ionic currents (BC gate status) showed that the kinetics of both slowed down in two distinct phases with increasing duration of the depolarizing prepulse. The biphasic slowing in VSD deactivation and BC gate closure was strongly correlated in time and magnitude. Simultaneous recordings of ionic currents and fluorescence from a probe tracking VSD movement in Shaker directly demonstrated that both processes were synchronized. Whereas the first slowing originates from a stabilization imposed by BC gate opening, the subsequent slowing reflects the rearrangement of the VSD toward its relaxed state (relaxation). The VSD relaxation was observed in the Ciona intestinalis voltage-sensitive phosphatase and in its isolated VSD. Collectively, our results show that the VSD relaxation is not kinetically related to C-type inactivation and is an intrinsic property of the VSD. We propose VSD relaxation as a general mechanism for depolarization-induced slowing of BC gate closure that may enable Kv1.2 channels to modulate the firing frequency of neurons based on the depolarization history.
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spelling pubmed-34831142013-05-01 Molecular mechanism for depolarization-induced modulation of Kv channel closure Labro, Alain J. Lacroix, Jerome J. Villalba-Galea, Carlos A. Snyders, Dirk J. Bezanilla, Francisco J Gen Physiol Article Voltage-dependent potassium (Kv) channels provide the repolarizing power that shapes the action potential duration and helps control the firing frequency of neurons. The K(+) permeation through the channel pore is controlled by an intracellularly located bundle-crossing (BC) gate that communicates with the voltage-sensing domains (VSDs). During prolonged membrane depolarizations, most Kv channels display C-type inactivation that halts K(+) conduction through constriction of the K(+) selectivity filter. Besides triggering C-type inactivation, we show that in Shaker and Kv1.2 channels (expressed in Xenopus laevis oocytes), prolonged membrane depolarizations also slow down the kinetics of VSD deactivation and BC gate closure during the subsequent membrane repolarization. Measurements of deactivating gating currents (reporting VSD movement) and ionic currents (BC gate status) showed that the kinetics of both slowed down in two distinct phases with increasing duration of the depolarizing prepulse. The biphasic slowing in VSD deactivation and BC gate closure was strongly correlated in time and magnitude. Simultaneous recordings of ionic currents and fluorescence from a probe tracking VSD movement in Shaker directly demonstrated that both processes were synchronized. Whereas the first slowing originates from a stabilization imposed by BC gate opening, the subsequent slowing reflects the rearrangement of the VSD toward its relaxed state (relaxation). The VSD relaxation was observed in the Ciona intestinalis voltage-sensitive phosphatase and in its isolated VSD. Collectively, our results show that the VSD relaxation is not kinetically related to C-type inactivation and is an intrinsic property of the VSD. We propose VSD relaxation as a general mechanism for depolarization-induced slowing of BC gate closure that may enable Kv1.2 channels to modulate the firing frequency of neurons based on the depolarization history. The Rockefeller University Press 2012-11 /pmc/articles/PMC3483114/ /pubmed/23071266 http://dx.doi.org/10.1085/jgp.201210817 Text en © 2012 Labro et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Labro, Alain J.
Lacroix, Jerome J.
Villalba-Galea, Carlos A.
Snyders, Dirk J.
Bezanilla, Francisco
Molecular mechanism for depolarization-induced modulation of Kv channel closure
title Molecular mechanism for depolarization-induced modulation of Kv channel closure
title_full Molecular mechanism for depolarization-induced modulation of Kv channel closure
title_fullStr Molecular mechanism for depolarization-induced modulation of Kv channel closure
title_full_unstemmed Molecular mechanism for depolarization-induced modulation of Kv channel closure
title_short Molecular mechanism for depolarization-induced modulation of Kv channel closure
title_sort molecular mechanism for depolarization-induced modulation of kv channel closure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483114/
https://www.ncbi.nlm.nih.gov/pubmed/23071266
http://dx.doi.org/10.1085/jgp.201210817
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