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Calcium channel gating

Tuned calcium entry through voltage-gated calcium channels is a key requirement for many cellular functions. This is ensured by channel gates which open during membrane depolarizations and seal the pore at rest. The gating process is determined by distinct sub-processes: movement of voltage-sensing...

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Autores principales: Hering, S., Zangerl-Plessl, E.-M., Beyl, S., Hohaus, A., Andranovits, S., Timin, E. N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096772/
https://www.ncbi.nlm.nih.gov/pubmed/29951751
http://dx.doi.org/10.1007/s00424-018-2163-7
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author Hering, S.
Zangerl-Plessl, E.-M.
Beyl, S.
Hohaus, A.
Andranovits, S.
Timin, E. N.
author_facet Hering, S.
Zangerl-Plessl, E.-M.
Beyl, S.
Hohaus, A.
Andranovits, S.
Timin, E. N.
author_sort Hering, S.
collection PubMed
description Tuned calcium entry through voltage-gated calcium channels is a key requirement for many cellular functions. This is ensured by channel gates which open during membrane depolarizations and seal the pore at rest. The gating process is determined by distinct sub-processes: movement of voltage-sensing domains (charged S4 segments) as well as opening and closure of S6 gates. Neutralization of S4 charges revealed that pore opening of CaV1.2 is triggered by a “gate releasing” movement of all four S4 segments with activation of IS4 (and IIIS4) being a rate-limiting stage. Segment IS4 additionally plays a crucial role in channel inactivation. Remarkably, S4 segments carrying only a single charged residue efficiently participate in gating. However, the complete set of S4 charges is required for stabilization of the open state. Voltage clamp fluorometry, the cryo-EM structure of a mammalian calcium channel, biophysical and pharmacological studies, and mathematical simulations have all contributed to a novel interpretation of the role of voltage sensors in channel opening, closure, and inactivation. We illustrate the role of the different methodologies in gating studies and discuss the key molecular events leading CaV channels to open and to close. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00424-018-2163-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-60967722018-08-24 Calcium channel gating Hering, S. Zangerl-Plessl, E.-M. Beyl, S. Hohaus, A. Andranovits, S. Timin, E. N. Pflugers Arch Invited Review Tuned calcium entry through voltage-gated calcium channels is a key requirement for many cellular functions. This is ensured by channel gates which open during membrane depolarizations and seal the pore at rest. The gating process is determined by distinct sub-processes: movement of voltage-sensing domains (charged S4 segments) as well as opening and closure of S6 gates. Neutralization of S4 charges revealed that pore opening of CaV1.2 is triggered by a “gate releasing” movement of all four S4 segments with activation of IS4 (and IIIS4) being a rate-limiting stage. Segment IS4 additionally plays a crucial role in channel inactivation. Remarkably, S4 segments carrying only a single charged residue efficiently participate in gating. However, the complete set of S4 charges is required for stabilization of the open state. Voltage clamp fluorometry, the cryo-EM structure of a mammalian calcium channel, biophysical and pharmacological studies, and mathematical simulations have all contributed to a novel interpretation of the role of voltage sensors in channel opening, closure, and inactivation. We illustrate the role of the different methodologies in gating studies and discuss the key molecular events leading CaV channels to open and to close. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00424-018-2163-7) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2018-06-27 2018 /pmc/articles/PMC6096772/ /pubmed/29951751 http://dx.doi.org/10.1007/s00424-018-2163-7 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.
spellingShingle Invited Review
Hering, S.
Zangerl-Plessl, E.-M.
Beyl, S.
Hohaus, A.
Andranovits, S.
Timin, E. N.
Calcium channel gating
title Calcium channel gating
title_full Calcium channel gating
title_fullStr Calcium channel gating
title_full_unstemmed Calcium channel gating
title_short Calcium channel gating
title_sort calcium channel gating
topic Invited Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096772/
https://www.ncbi.nlm.nih.gov/pubmed/29951751
http://dx.doi.org/10.1007/s00424-018-2163-7
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