Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotonia
The function of the chloride channel ClC-1 is crucial for the control of muscle excitability. Thus, reduction of ClC-1 functions by CLCN1 mutations leads to myotonia congenita. Many different animal models have contributed to understanding the myotonia pathophysiology. However, these models do not a...
| Autores: | , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2024 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositório: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:dnet:recercat____::cb8fe32be2ff0800ec87eb425d14d50a |
| Acesso em linha: | https://hdl.handle.net/2445/229705 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Fisiologia animal Músculs Canals de clorur Animal physiology Muscles Chloride channels |
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Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotoniaGaitán-Peñas, HéctorPerez-Rius, CarlaMuhaisen, AshrafCastellanos, AidaErrasti-Murugarren, EkaitzBarrallo-Gimeno, AlejandroAlcaraz-Perez, FranciscaEstévez Povedano, RaúlFisiologia animalMúsculsCanals de clorurAnimal physiologyMusclesChloride channelsThe function of the chloride channel ClC-1 is crucial for the control of muscle excitability. Thus, reduction of ClC-1 functions by CLCN1 mutations leads to myotonia congenita. Many different animal models have contributed to understanding the myotonia pathophysiology. However, these models do not allow in vivo screening of potentially therapeutic drugs, as the zebrafish model does. In this work, we identified and characterized the two zebrafish orthologues (clc-1a and clc-1b) of the ClC-1 channel. Both channels are mostly expressed in the skeletal muscle as revealed by RT-PCR, western blot, and electrophysiological recordings of myotubes, and clc-1a is predominantly expressed in adult stages. Characterization in Xenopus oocytes shows that the zebrafish channels display similar anion selectivity and voltage dependence to their human counterparts. However, they show reduced sensitivity to the inhibitor 9-anthracenecarboxylic acid (9-AC), and acidic pH inverts the voltage dependence of activation. Reduction of clc-1a/b expression hampers spontaneous and mechanically stimulated movement, which could be reverted by expression of human ClC-1 but not by some ClC-1 containing myotonia mutations. Treatment of clc-1-depleted zebrafish with mexiletine, a typical drug used in human myotonia, improves the motor behaviour. Our work extends the repertoire of ClC channels to evolutionary structure–function studies and proposes the zebrafish clcn1 crispant model as a simple tool to find novel therapies for myotonia.The Physiological Society2026202620242026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion20 p.application/pdfhttps://hdl.handle.net/2445/229705Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1113/JP286530Journal of Physiology, 2024, vol. 602, num.16, p. 3975-3994https://doi.org/10.1113/JP286530cc-by-nc-nd (c) Gaitán-Peñas, Héctor et al., 2024https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:recercat____::cb8fe32be2ff0800ec87eb425d14d50a2026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotonia |
| title |
Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotonia |
| spellingShingle |
Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotonia Gaitán-Peñas, Héctor Fisiologia animal Músculs Canals de clorur Animal physiology Muscles Chloride channels |
| title_short |
Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotonia |
| title_full |
Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotonia |
| title_fullStr |
Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotonia |
| title_full_unstemmed |
Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotonia |
| title_sort |
Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotonia |
| dc.creator.none.fl_str_mv |
Gaitán-Peñas, Héctor Perez-Rius, Carla Muhaisen, Ashraf Castellanos, Aida Errasti-Murugarren, Ekaitz Barrallo-Gimeno, Alejandro Alcaraz-Perez, Francisca Estévez Povedano, Raúl |
| author |
Gaitán-Peñas, Héctor |
| author_facet |
Gaitán-Peñas, Héctor Perez-Rius, Carla Muhaisen, Ashraf Castellanos, Aida Errasti-Murugarren, Ekaitz Barrallo-Gimeno, Alejandro Alcaraz-Perez, Francisca Estévez Povedano, Raúl |
| author_role |
author |
| author2 |
Perez-Rius, Carla Muhaisen, Ashraf Castellanos, Aida Errasti-Murugarren, Ekaitz Barrallo-Gimeno, Alejandro Alcaraz-Perez, Francisca Estévez Povedano, Raúl |
| author2_role |
author author author author author author author |
| dc.subject.none.fl_str_mv |
Fisiologia animal Músculs Canals de clorur Animal physiology Muscles Chloride channels |
| topic |
Fisiologia animal Músculs Canals de clorur Animal physiology Muscles Chloride channels |
| description |
The function of the chloride channel ClC-1 is crucial for the control of muscle excitability. Thus, reduction of ClC-1 functions by CLCN1 mutations leads to myotonia congenita. Many different animal models have contributed to understanding the myotonia pathophysiology. However, these models do not allow in vivo screening of potentially therapeutic drugs, as the zebrafish model does. In this work, we identified and characterized the two zebrafish orthologues (clc-1a and clc-1b) of the ClC-1 channel. Both channels are mostly expressed in the skeletal muscle as revealed by RT-PCR, western blot, and electrophysiological recordings of myotubes, and clc-1a is predominantly expressed in adult stages. Characterization in Xenopus oocytes shows that the zebrafish channels display similar anion selectivity and voltage dependence to their human counterparts. However, they show reduced sensitivity to the inhibitor 9-anthracenecarboxylic acid (9-AC), and acidic pH inverts the voltage dependence of activation. Reduction of clc-1a/b expression hampers spontaneous and mechanically stimulated movement, which could be reverted by expression of human ClC-1 but not by some ClC-1 containing myotonia mutations. Treatment of clc-1-depleted zebrafish with mexiletine, a typical drug used in human myotonia, improves the motor behaviour. Our work extends the repertoire of ClC channels to evolutionary structure–function studies and proposes the zebrafish clcn1 crispant model as a simple tool to find novel therapies for myotonia. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2026 2026 2026 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/229705 |
| url |
https://hdl.handle.net/2445/229705 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1113/JP286530 Journal of Physiology, 2024, vol. 602, num.16, p. 3975-3994 https://doi.org/10.1113/JP286530 |
| dc.rights.none.fl_str_mv |
cc-by-nc-nd (c) Gaitán-Peñas, Héctor et al., 2024 https://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by-nc-nd (c) Gaitán-Peñas, Héctor et al., 2024 https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
20 p. application/pdf |
| dc.publisher.none.fl_str_mv |
The Physiological Society |
| publisher.none.fl_str_mv |
The Physiological Society |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Ciències Fisiològiques) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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