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A novel phospho-modulatory mechanism contributes to the calcium-dependent regulation of T-type Ca(2+) channels
Ca(v)3 / T-type Ca(2+) channels are dynamically regulated by intracellular Ca(2+) ions, which inhibit Ca(v)3 availability. Here, we demonstrate that this inhibition becomes irreversible in the presence of non-hydrolysable ATP analogs, resulting in a strong hyperpolarizing shift in the steady-state i...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821770/ https://www.ncbi.nlm.nih.gov/pubmed/31666636 http://dx.doi.org/10.1038/s41598-019-52194-6 |
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author | Chemin, Jean Stamenic, Tamara Timic Cazade, Magalie Llinares, Jodie Blesneac, Iulia Todorovic, Slobodan M. Lory, Philippe |
author_facet | Chemin, Jean Stamenic, Tamara Timic Cazade, Magalie Llinares, Jodie Blesneac, Iulia Todorovic, Slobodan M. Lory, Philippe |
author_sort | Chemin, Jean |
collection | PubMed |
description | Ca(v)3 / T-type Ca(2+) channels are dynamically regulated by intracellular Ca(2+) ions, which inhibit Ca(v)3 availability. Here, we demonstrate that this inhibition becomes irreversible in the presence of non-hydrolysable ATP analogs, resulting in a strong hyperpolarizing shift in the steady-state inactivation of the residual Ca(v)3 current. Importantly, the effect of these ATP analogs was prevented in the presence of intracellular BAPTA. Additional findings obtained using intracellular dialysis of inorganic phosphate and alkaline phosphatase or NaN(3) treatment further support the involvement of a phosphorylation mechanism. Contrasting with Ca(v)1 and Ca(v)2 Ca(2+) channels, the Ca(2+)-dependent modulation of Ca(v)3 channels appears to be independent of calmodulin, calcineurin and endocytic pathways. Similar findings were obtained for the native T-type Ca(2+) current recorded in rat thalamic neurons of the central medial nucleus. Overall, our data reveal a new Ca(2+) sensitive phosphorylation-dependent mechanism regulating Ca(v)3 channels, with potentially important physiological implications for the multiple cell functions controlled by T-type Ca(2+) channels. |
format | Online Article Text |
id | pubmed-6821770 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68217702019-11-05 A novel phospho-modulatory mechanism contributes to the calcium-dependent regulation of T-type Ca(2+) channels Chemin, Jean Stamenic, Tamara Timic Cazade, Magalie Llinares, Jodie Blesneac, Iulia Todorovic, Slobodan M. Lory, Philippe Sci Rep Article Ca(v)3 / T-type Ca(2+) channels are dynamically regulated by intracellular Ca(2+) ions, which inhibit Ca(v)3 availability. Here, we demonstrate that this inhibition becomes irreversible in the presence of non-hydrolysable ATP analogs, resulting in a strong hyperpolarizing shift in the steady-state inactivation of the residual Ca(v)3 current. Importantly, the effect of these ATP analogs was prevented in the presence of intracellular BAPTA. Additional findings obtained using intracellular dialysis of inorganic phosphate and alkaline phosphatase or NaN(3) treatment further support the involvement of a phosphorylation mechanism. Contrasting with Ca(v)1 and Ca(v)2 Ca(2+) channels, the Ca(2+)-dependent modulation of Ca(v)3 channels appears to be independent of calmodulin, calcineurin and endocytic pathways. Similar findings were obtained for the native T-type Ca(2+) current recorded in rat thalamic neurons of the central medial nucleus. Overall, our data reveal a new Ca(2+) sensitive phosphorylation-dependent mechanism regulating Ca(v)3 channels, with potentially important physiological implications for the multiple cell functions controlled by T-type Ca(2+) channels. Nature Publishing Group UK 2019-10-30 /pmc/articles/PMC6821770/ /pubmed/31666636 http://dx.doi.org/10.1038/s41598-019-52194-6 Text en © The Author(s) 2019 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 Chemin, Jean Stamenic, Tamara Timic Cazade, Magalie Llinares, Jodie Blesneac, Iulia Todorovic, Slobodan M. Lory, Philippe A novel phospho-modulatory mechanism contributes to the calcium-dependent regulation of T-type Ca(2+) channels |
title | A novel phospho-modulatory mechanism contributes to the calcium-dependent regulation of T-type Ca(2+) channels |
title_full | A novel phospho-modulatory mechanism contributes to the calcium-dependent regulation of T-type Ca(2+) channels |
title_fullStr | A novel phospho-modulatory mechanism contributes to the calcium-dependent regulation of T-type Ca(2+) channels |
title_full_unstemmed | A novel phospho-modulatory mechanism contributes to the calcium-dependent regulation of T-type Ca(2+) channels |
title_short | A novel phospho-modulatory mechanism contributes to the calcium-dependent regulation of T-type Ca(2+) channels |
title_sort | novel phospho-modulatory mechanism contributes to the calcium-dependent regulation of t-type ca(2+) channels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821770/ https://www.ncbi.nlm.nih.gov/pubmed/31666636 http://dx.doi.org/10.1038/s41598-019-52194-6 |
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