Cargando…
Mechanism of voltage sensing in Ca(2+)- and voltage-activated K(+) (BK) channels
In neurosecretion, allosteric communication between voltage sensors and Ca(2+) binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231616/ https://www.ncbi.nlm.nih.gov/pubmed/35704760 http://dx.doi.org/10.1073/pnas.2204620119 |
_version_ | 1784735385842089984 |
---|---|
author | Carrasquel-Ursulaez, Willy Segura, Ignacio Díaz-Franulic, Ignacio Márquez-Miranda, Valeria Echeverría, Felipe Lorenzo-Ceballos, Yenisleidy Espinoza, Nicolás Rojas, Maximiliano Garate, Jose Antonio Perozo, Eduardo Alvarez, Osvaldo Gonzalez-Nilo, Fernando D. Latorre, Ramón |
author_facet | Carrasquel-Ursulaez, Willy Segura, Ignacio Díaz-Franulic, Ignacio Márquez-Miranda, Valeria Echeverría, Felipe Lorenzo-Ceballos, Yenisleidy Espinoza, Nicolás Rojas, Maximiliano Garate, Jose Antonio Perozo, Eduardo Alvarez, Osvaldo Gonzalez-Nilo, Fernando D. Latorre, Ramón |
author_sort | Carrasquel-Ursulaez, Willy |
collection | PubMed |
description | In neurosecretion, allosteric communication between voltage sensors and Ca(2+) binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. Significantly, the energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). Molecular dynamics simulations and proton transport experiments in the hyperpolarization-activated R210H mutant suggest that the electric field drops off within a narrow septum whose boundaries are defined by the gating charges. Unlike Kv channels, the charge movement in BK appears to be limited to a small displacement of the guanidinium moieties of R210 and R213, without significant movement of the S4. |
format | Online Article Text |
id | pubmed-9231616 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-92316162022-07-25 Mechanism of voltage sensing in Ca(2+)- and voltage-activated K(+) (BK) channels Carrasquel-Ursulaez, Willy Segura, Ignacio Díaz-Franulic, Ignacio Márquez-Miranda, Valeria Echeverría, Felipe Lorenzo-Ceballos, Yenisleidy Espinoza, Nicolás Rojas, Maximiliano Garate, Jose Antonio Perozo, Eduardo Alvarez, Osvaldo Gonzalez-Nilo, Fernando D. Latorre, Ramón Proc Natl Acad Sci U S A Biological Sciences In neurosecretion, allosteric communication between voltage sensors and Ca(2+) binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. Significantly, the energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). Molecular dynamics simulations and proton transport experiments in the hyperpolarization-activated R210H mutant suggest that the electric field drops off within a narrow septum whose boundaries are defined by the gating charges. Unlike Kv channels, the charge movement in BK appears to be limited to a small displacement of the guanidinium moieties of R210 and R213, without significant movement of the S4. National Academy of Sciences 2022-06-15 2022-06-21 /pmc/articles/PMC9231616/ /pubmed/35704760 http://dx.doi.org/10.1073/pnas.2204620119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Carrasquel-Ursulaez, Willy Segura, Ignacio Díaz-Franulic, Ignacio Márquez-Miranda, Valeria Echeverría, Felipe Lorenzo-Ceballos, Yenisleidy Espinoza, Nicolás Rojas, Maximiliano Garate, Jose Antonio Perozo, Eduardo Alvarez, Osvaldo Gonzalez-Nilo, Fernando D. Latorre, Ramón Mechanism of voltage sensing in Ca(2+)- and voltage-activated K(+) (BK) channels |
title | Mechanism of voltage sensing in Ca(2+)- and voltage-activated K(+) (BK) channels |
title_full | Mechanism of voltage sensing in Ca(2+)- and voltage-activated K(+) (BK) channels |
title_fullStr | Mechanism of voltage sensing in Ca(2+)- and voltage-activated K(+) (BK) channels |
title_full_unstemmed | Mechanism of voltage sensing in Ca(2+)- and voltage-activated K(+) (BK) channels |
title_short | Mechanism of voltage sensing in Ca(2+)- and voltage-activated K(+) (BK) channels |
title_sort | mechanism of voltage sensing in ca(2+)- and voltage-activated k(+) (bk) channels |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231616/ https://www.ncbi.nlm.nih.gov/pubmed/35704760 http://dx.doi.org/10.1073/pnas.2204620119 |
work_keys_str_mv | AT carrasquelursulaezwilly mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT seguraignacio mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT diazfranulicignacio mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT marquezmirandavaleria mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT echeverriafelipe mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT lorenzoceballosyenisleidy mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT espinozanicolas mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT rojasmaximiliano mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT garatejoseantonio mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT perozoeduardo mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT alvarezosvaldo mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT gonzaleznilofernandod mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels AT latorreramon mechanismofvoltagesensinginca2andvoltageactivatedkbkchannels |