TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity

Background potassium-permeable ion channels play a critical role in tuning the excitability of nociceptors, yet the precise role played by different subsets of channels is not fully understood. Decreases in TRESK (TWIK-related spinal cord K+ channel) expression/function enhance sensory neurons excit...

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Autores: Castellanos, Aida, Pujol Coma, Anna, Andres, Alba, Negm, Ahmed, Callejo, Gerard, Soto del Cerro, David, Noel, Jacques, Comes i Beltrán, Núria, Gasull Casanova, Xavier
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/183514
Acceso en línea:https://hdl.handle.net/2445/183514
Access Level:acceso abierto
Palabra clave:Canals de potassi
Neurofisiologia
Potassium channels
Neurophysiology
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spelling TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivityCastellanos, AidaPujol Coma, AnnaAndres, AlbaNegm, AhmedCallejo, GerardSoto del Cerro, DavidNoel, JacquesComes i Beltrán, NúriaGasull Casanova, XavierCanals de potassiNeurofisiologiaPotassium channelsNeurophysiologyBackground potassium-permeable ion channels play a critical role in tuning the excitability of nociceptors, yet the precise role played by different subsets of channels is not fully understood. Decreases in TRESK (TWIK-related spinal cord K+ channel) expression/function enhance sensory neurons excitability, but its role in somatosensory perception and nociception is poorly understood. Here, we used a TRESK knockout (KO) mouse to address these questions. We show that TRESK regulates the sensitivity of sensory neurons in a modality-specific manner, contributing to mechanical and cold sensitivity but without any effect on heat sensitivity. Nociceptive neurons isolated from TRESK KO mice show a decreased threshold for activation and skin nociceptive C-fibers show an enhanced activation by cold and mechanical stimulation that was also observed in behavioral tests in vivo. TRESK is also involved in osmotic pain and in early phases of formalin-induced inflammatory pain, but not in the development of mechanical and heat hyperalgesia during chronic pain. In contrast, mice lacking TRESK present cold allodynia that is not further enhanced by oxaliplatin. In summary, genetic removal of TRESK uncovers enhanced mechanical and cold sensitivity, indicating that the channel regulates the excitability of specific neuronal subpopulations involved in mechanosensitivity and cold-sensing, acting as a brake to prevent activation by innocuous stimuli.The Physiological Society2022202220202022info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion62 p.application/pdfhttps://hdl.handle.net/2445/183514Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1113/JP279203Journal of Physiology, 2020, vol. 598, num. 5, p. 1017-1038https://doi.org/10.1113/JP279203(c) Castellanos, Aida et al., 2020info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1835142026-05-29T05:05:01Z
dc.title.none.fl_str_mv TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity
title TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity
spellingShingle TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity
Castellanos, Aida
Canals de potassi
Neurofisiologia
Potassium channels
Neurophysiology
title_short TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity
title_full TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity
title_fullStr TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity
title_full_unstemmed TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity
title_sort TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity
dc.creator.none.fl_str_mv Castellanos, Aida
Pujol Coma, Anna
Andres, Alba
Negm, Ahmed
Callejo, Gerard
Soto del Cerro, David
Noel, Jacques
Comes i Beltrán, Núria
Gasull Casanova, Xavier
author Castellanos, Aida
author_facet Castellanos, Aida
Pujol Coma, Anna
Andres, Alba
Negm, Ahmed
Callejo, Gerard
Soto del Cerro, David
Noel, Jacques
Comes i Beltrán, Núria
Gasull Casanova, Xavier
author_role author
author2 Pujol Coma, Anna
Andres, Alba
Negm, Ahmed
Callejo, Gerard
Soto del Cerro, David
Noel, Jacques
Comes i Beltrán, Núria
Gasull Casanova, Xavier
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Canals de potassi
Neurofisiologia
Potassium channels
Neurophysiology
topic Canals de potassi
Neurofisiologia
Potassium channels
Neurophysiology
description Background potassium-permeable ion channels play a critical role in tuning the excitability of nociceptors, yet the precise role played by different subsets of channels is not fully understood. Decreases in TRESK (TWIK-related spinal cord K+ channel) expression/function enhance sensory neurons excitability, but its role in somatosensory perception and nociception is poorly understood. Here, we used a TRESK knockout (KO) mouse to address these questions. We show that TRESK regulates the sensitivity of sensory neurons in a modality-specific manner, contributing to mechanical and cold sensitivity but without any effect on heat sensitivity. Nociceptive neurons isolated from TRESK KO mice show a decreased threshold for activation and skin nociceptive C-fibers show an enhanced activation by cold and mechanical stimulation that was also observed in behavioral tests in vivo. TRESK is also involved in osmotic pain and in early phases of formalin-induced inflammatory pain, but not in the development of mechanical and heat hyperalgesia during chronic pain. In contrast, mice lacking TRESK present cold allodynia that is not further enhanced by oxaliplatin. In summary, genetic removal of TRESK uncovers enhanced mechanical and cold sensitivity, indicating that the channel regulates the excitability of specific neuronal subpopulations involved in mechanosensitivity and cold-sensing, acting as a brake to prevent activation by innocuous stimuli.
publishDate 2020
dc.date.none.fl_str_mv 2020
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/183514
url https://hdl.handle.net/2445/183514
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1113/JP279203
Journal of Physiology, 2020, vol. 598, num. 5, p. 1017-1038
https://doi.org/10.1113/JP279203
dc.rights.none.fl_str_mv (c) Castellanos, Aida et al., 2020
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Castellanos, Aida et al., 2020
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 62 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 (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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