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Constitutive Activation of the Shaker Kv Channel

In different types of K(+) channels the primary activation gate is thought to reside near the intracellular entrance to the ion conduction pore. In the Shaker Kv channel the gate is closed at negative membrane voltages, but can be opened with membrane depolarization. In a previous study of the S6 ac...

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Autores principales: Sukhareva, Manana, Hackos, David H., Swartz, Kenton J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2229584/
https://www.ncbi.nlm.nih.gov/pubmed/14557403
http://dx.doi.org/10.1085/jgp.200308905
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author Sukhareva, Manana
Hackos, David H.
Swartz, Kenton J.
author_facet Sukhareva, Manana
Hackos, David H.
Swartz, Kenton J.
author_sort Sukhareva, Manana
collection PubMed
description In different types of K(+) channels the primary activation gate is thought to reside near the intracellular entrance to the ion conduction pore. In the Shaker Kv channel the gate is closed at negative membrane voltages, but can be opened with membrane depolarization. In a previous study of the S6 activation gate in Shaker (Hackos, D.H., T.H. Chang, and K.J. Swartz. 2002. J. Gen. Physiol. 119:521–532.), we found that mutation of Pro 475 to Asp results in a channel that displays a large macroscopic conductance at negative membrane voltages, with only small increases in conductance with membrane depolarization. In the present study we explore the mechanism underlying this constitutively conducting phenotype using both macroscopic and single-channel recordings, and probes that interact with the voltage sensors or the intracellular entrance to the ion conduction pore. Our results suggest that constitutive conduction results from a dramatic perturbation of the closed-open equilibrium, enabling opening of the activation gate without voltage-sensor activation. This mechanism is discussed in the context of allosteric models for activation of Kv channels and what is known about the structure of this critical region in K(+) channels.
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spelling pubmed-22295842008-04-16 Constitutive Activation of the Shaker Kv Channel Sukhareva, Manana Hackos, David H. Swartz, Kenton J. J Gen Physiol Article In different types of K(+) channels the primary activation gate is thought to reside near the intracellular entrance to the ion conduction pore. In the Shaker Kv channel the gate is closed at negative membrane voltages, but can be opened with membrane depolarization. In a previous study of the S6 activation gate in Shaker (Hackos, D.H., T.H. Chang, and K.J. Swartz. 2002. J. Gen. Physiol. 119:521–532.), we found that mutation of Pro 475 to Asp results in a channel that displays a large macroscopic conductance at negative membrane voltages, with only small increases in conductance with membrane depolarization. In the present study we explore the mechanism underlying this constitutively conducting phenotype using both macroscopic and single-channel recordings, and probes that interact with the voltage sensors or the intracellular entrance to the ion conduction pore. Our results suggest that constitutive conduction results from a dramatic perturbation of the closed-open equilibrium, enabling opening of the activation gate without voltage-sensor activation. This mechanism is discussed in the context of allosteric models for activation of Kv channels and what is known about the structure of this critical region in K(+) channels. The Rockefeller University Press 2003-11 /pmc/articles/PMC2229584/ /pubmed/14557403 http://dx.doi.org/10.1085/jgp.200308905 Text en Copyright © 2003, 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
Sukhareva, Manana
Hackos, David H.
Swartz, Kenton J.
Constitutive Activation of the Shaker Kv Channel
title Constitutive Activation of the Shaker Kv Channel
title_full Constitutive Activation of the Shaker Kv Channel
title_fullStr Constitutive Activation of the Shaker Kv Channel
title_full_unstemmed Constitutive Activation of the Shaker Kv Channel
title_short Constitutive Activation of the Shaker Kv Channel
title_sort constitutive activation of the shaker kv channel
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2229584/
https://www.ncbi.nlm.nih.gov/pubmed/14557403
http://dx.doi.org/10.1085/jgp.200308905
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