Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pinto, Bernardo I., Pupo, Amaury, García, Isaac E., Mena-Ulecia, Karel, Martínez, Agustín D., Latorre, Ramón, Gonzalez, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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
_version_ 1783280456622407680
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
work_keys_str_mv AT pintobernardoi calciumbindingandvoltagegatingincx46hemichannels
AT pupoamaury calciumbindingandvoltagegatingincx46hemichannels
AT garciaisaace calciumbindingandvoltagegatingincx46hemichannels
AT menauleciakarel calciumbindingandvoltagegatingincx46hemichannels
AT martinezagustind calciumbindingandvoltagegatingincx46hemichannels
AT latorreramon calciumbindingandvoltagegatingincx46hemichannels
AT gonzalezcarlos calciumbindingandvoltagegatingincx46hemichannels