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Calcium binding and voltage gating in Cx46 hemichannels
The opening of connexin (Cx) hemichannels in the membrane is tightly regulated by calcium (Ca(2+)) and membrane voltage. Electrophysiological and atomic force microscopy experiments indicate that Ca(2+) stabilizes the hemichannel closed state. However, structural data show that Ca(2+) binding induce...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696461/ https://www.ncbi.nlm.nih.gov/pubmed/29158540 http://dx.doi.org/10.1038/s41598-017-15975-5 |
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author | Pinto, Bernardo I. Pupo, Amaury García, Isaac E. Mena-Ulecia, Karel Martínez, Agustín D. Latorre, Ramón Gonzalez, Carlos |
author_facet | Pinto, Bernardo I. Pupo, Amaury García, Isaac E. Mena-Ulecia, Karel Martínez, Agustín D. Latorre, Ramón Gonzalez, Carlos |
author_sort | Pinto, Bernardo I. |
collection | PubMed |
description | The opening of connexin (Cx) hemichannels in the membrane is tightly regulated by calcium (Ca(2+)) and membrane voltage. Electrophysiological and atomic force microscopy experiments indicate that Ca(2+) stabilizes the hemichannel closed state. However, structural data show that Ca(2+) binding induces an electrostatic seal preventing ion transport without significant structural rearrangements. In agreement with the closed-state stabilization hypothesis, we found that the apparent Ca(2+) sensitivity is increased as the voltage is made more negative. Moreover, the voltage and Ca(2+) dependence of the channel kinetics indicate that the voltage sensor movement and Ca(2+) binding are allosterically coupled. An allosteric kinetic model in which the Ca(2+) decreases the energy necessary to deactivate the voltage sensor reproduces the effects of Ca(2+) and voltage in Cx46 hemichannels. In agreement with the model and suggesting a conformational change that narrows the pore, Ca(2+) inhibits the water flux through Cx hemichannels. We conclude that Ca(2+) and voltage act allosterically to stabilize the closed conformation of Cx46 hemichannels. |
format | Online Article Text |
id | pubmed-5696461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56964612017-11-29 Calcium binding and voltage gating in Cx46 hemichannels Pinto, Bernardo I. Pupo, Amaury García, Isaac E. Mena-Ulecia, Karel Martínez, Agustín D. Latorre, Ramón Gonzalez, Carlos Sci Rep Article The opening of connexin (Cx) hemichannels in the membrane is tightly regulated by calcium (Ca(2+)) and membrane voltage. Electrophysiological and atomic force microscopy experiments indicate that Ca(2+) stabilizes the hemichannel closed state. However, structural data show that Ca(2+) binding induces an electrostatic seal preventing ion transport without significant structural rearrangements. In agreement with the closed-state stabilization hypothesis, we found that the apparent Ca(2+) sensitivity is increased as the voltage is made more negative. Moreover, the voltage and Ca(2+) dependence of the channel kinetics indicate that the voltage sensor movement and Ca(2+) binding are allosterically coupled. An allosteric kinetic model in which the Ca(2+) decreases the energy necessary to deactivate the voltage sensor reproduces the effects of Ca(2+) and voltage in Cx46 hemichannels. In agreement with the model and suggesting a conformational change that narrows the pore, Ca(2+) inhibits the water flux through Cx hemichannels. We conclude that Ca(2+) and voltage act allosterically to stabilize the closed conformation of Cx46 hemichannels. Nature Publishing Group UK 2017-11-20 /pmc/articles/PMC5696461/ /pubmed/29158540 http://dx.doi.org/10.1038/s41598-017-15975-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Pinto, Bernardo I. Pupo, Amaury García, Isaac E. Mena-Ulecia, Karel Martínez, Agustín D. Latorre, Ramón Gonzalez, Carlos Calcium binding and voltage gating in Cx46 hemichannels |
title | Calcium binding and voltage gating in Cx46 hemichannels |
title_full | Calcium binding and voltage gating in Cx46 hemichannels |
title_fullStr | Calcium binding and voltage gating in Cx46 hemichannels |
title_full_unstemmed | Calcium binding and voltage gating in Cx46 hemichannels |
title_short | Calcium binding and voltage gating in Cx46 hemichannels |
title_sort | calcium binding and voltage gating in cx46 hemichannels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696461/ https://www.ncbi.nlm.nih.gov/pubmed/29158540 http://dx.doi.org/10.1038/s41598-017-15975-5 |
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