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Molecular mechanism of voltage sensing in voltage-gated proton channels
Voltage-gated proton (Hv) channels play an essential role in phagocytic cells by generating a hyperpolarizing proton current that electrically compensates for the depolarizing current generated by the NADPH oxidase during the respiratory burst, thereby ensuring a sustained production of reactive oxy...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581690/ https://www.ncbi.nlm.nih.gov/pubmed/23401575 http://dx.doi.org/10.1085/jgp.201210857 |
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author | Gonzalez, Carlos Rebolledo, Santiago Perez, Marta E. Larsson, H. Peter |
author_facet | Gonzalez, Carlos Rebolledo, Santiago Perez, Marta E. Larsson, H. Peter |
author_sort | Gonzalez, Carlos |
collection | PubMed |
description | Voltage-gated proton (Hv) channels play an essential role in phagocytic cells by generating a hyperpolarizing proton current that electrically compensates for the depolarizing current generated by the NADPH oxidase during the respiratory burst, thereby ensuring a sustained production of reactive oxygen species by the NADPH oxidase in phagocytes to neutralize engulfed bacteria. Despite the importance of the voltage-dependent Hv current, it is at present unclear which residues in Hv channels are responsible for the voltage activation. Here we show that individual neutralizations of three charged residues in the fourth transmembrane domain, S4, all reduce the voltage dependence of activation. In addition, we show that the middle S4 charged residue moves from a position accessible from the cytosolic solution to a position accessible from the extracellular solution, suggesting that this residue moves across most of the membrane electric field during voltage activation of Hv channels. Our results show for the first time that the charge movement of these three S4 charges accounts for almost all of the measured gating charge in Hv channels. |
format | Online Article Text |
id | pubmed-3581690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35816902013-09-01 Molecular mechanism of voltage sensing in voltage-gated proton channels Gonzalez, Carlos Rebolledo, Santiago Perez, Marta E. Larsson, H. Peter J Gen Physiol Research Article Voltage-gated proton (Hv) channels play an essential role in phagocytic cells by generating a hyperpolarizing proton current that electrically compensates for the depolarizing current generated by the NADPH oxidase during the respiratory burst, thereby ensuring a sustained production of reactive oxygen species by the NADPH oxidase in phagocytes to neutralize engulfed bacteria. Despite the importance of the voltage-dependent Hv current, it is at present unclear which residues in Hv channels are responsible for the voltage activation. Here we show that individual neutralizations of three charged residues in the fourth transmembrane domain, S4, all reduce the voltage dependence of activation. In addition, we show that the middle S4 charged residue moves from a position accessible from the cytosolic solution to a position accessible from the extracellular solution, suggesting that this residue moves across most of the membrane electric field during voltage activation of Hv channels. Our results show for the first time that the charge movement of these three S4 charges accounts for almost all of the measured gating charge in Hv channels. The Rockefeller University Press 2013-03 /pmc/articles/PMC3581690/ /pubmed/23401575 http://dx.doi.org/10.1085/jgp.201210857 Text en © 2013 Gonzalez 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 | Research Article Gonzalez, Carlos Rebolledo, Santiago Perez, Marta E. Larsson, H. Peter Molecular mechanism of voltage sensing in voltage-gated proton channels |
title | Molecular mechanism of voltage sensing in voltage-gated proton channels |
title_full | Molecular mechanism of voltage sensing in voltage-gated proton channels |
title_fullStr | Molecular mechanism of voltage sensing in voltage-gated proton channels |
title_full_unstemmed | Molecular mechanism of voltage sensing in voltage-gated proton channels |
title_short | Molecular mechanism of voltage sensing in voltage-gated proton channels |
title_sort | molecular mechanism of voltage sensing in voltage-gated proton channels |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581690/ https://www.ncbi.nlm.nih.gov/pubmed/23401575 http://dx.doi.org/10.1085/jgp.201210857 |
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