Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus

Autores
Cozart, Michael A.; Phelan, Kevin D.; Wu, Hong; Mu, Shengyu; Birnbaumer, Lutz; Rusch, Nancy J.; Zheng, Fang
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Human status epilepticus (SE) is associated with a pathological reduction in cerebral blood flow termed the inverse hemodynamic response (IHR). Canonical transient receptor potential 3 (TRPC3) channels are integral to the propagation of seizures in SE, and vascular smooth muscle cell (VSMC) TRPC3 channels participate in vasoconstriction. Therefore, we hypothesize that cerebrovascular TRPC3 channels may contribute to seizure-induced IHR. To examine this possibility, we developed a smooth muscle-specific TRPC3 knockout (TRPC3smcKO) mouse. To quantify changes in neurovascular coupling, we combined laser speckle contrast imaging with simultaneous electroencephalogram recordings. Control mice exhibited multiple IHRs, and a limited increase in cerebral blood flow during SE with a high degree of moment-to-moment variability in which blood flow was not correlated with neuronal activity. In contrast, TRPC3smcKO mice showed a greater increase in blood flow that was less variable and was positively correlated with neuronal activity. Genetic ablation of smooth muscle TRPC3 channels shortened the duration of SE by eliminating a secondary phase of intense seizures, which was evident in littermate controls. Our results are consistent with the idea that TRPC3 channels expressed by cerebral VSMCs contribute to the IHR during SE, which is a critical factor in the progression of SE.
Fil: Cozart, Michael A.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Phelan, Kevin D.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Wu, Hong. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Mu, Shengyu. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Rusch, Nancy J.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Zheng, Fang. University of Arkansas for Medical Sciences; Estados Unidos
Materia
TRPC3
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/141701
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticusCozart, Michael A.Phelan, Kevin D.Wu, HongMu, ShengyuBirnbaumer, LutzRusch, Nancy J.Zheng, FangTRPC3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Human status epilepticus (SE) is associated with a pathological reduction in cerebral blood flow termed the inverse hemodynamic response (IHR). Canonical transient receptor potential 3 (TRPC3) channels are integral to the propagation of seizures in SE, and vascular smooth muscle cell (VSMC) TRPC3 channels participate in vasoconstriction. Therefore, we hypothesize that cerebrovascular TRPC3 channels may contribute to seizure-induced IHR. To examine this possibility, we developed a smooth muscle-specific TRPC3 knockout (TRPC3smcKO) mouse. To quantify changes in neurovascular coupling, we combined laser speckle contrast imaging with simultaneous electroencephalogram recordings. Control mice exhibited multiple IHRs, and a limited increase in cerebral blood flow during SE with a high degree of moment-to-moment variability in which blood flow was not correlated with neuronal activity. In contrast, TRPC3smcKO mice showed a greater increase in blood flow that was less variable and was positively correlated with neuronal activity. Genetic ablation of smooth muscle TRPC3 channels shortened the duration of SE by eliminating a secondary phase of intense seizures, which was evident in littermate controls. Our results are consistent with the idea that TRPC3 channels expressed by cerebral VSMCs contribute to the IHR during SE, which is a critical factor in the progression of SE.Fil: Cozart, Michael A.. University of Arkansas for Medical Sciences; Estados UnidosFil: Phelan, Kevin D.. University of Arkansas for Medical Sciences; Estados UnidosFil: Wu, Hong. University of Arkansas for Medical Sciences; Estados UnidosFil: Mu, Shengyu. University of Arkansas for Medical Sciences; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Rusch, Nancy J.. University of Arkansas for Medical Sciences; Estados UnidosFil: Zheng, Fang. University of Arkansas for Medical Sciences; Estados UnidosNature2020-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/141701Cozart, Michael A.; Phelan, Kevin D.; Wu, Hong; Mu, Shengyu; Birnbaumer, Lutz; et al.; Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus; Nature; Scientific Reports; 10; 1; 12-2020; 1-101476-46872045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-57733-0info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-020-57733-0info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:09:17Zoai:ri.conicet.gov.ar:11336/141701instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:09:17.457CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus
title Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus
spellingShingle Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus
Cozart, Michael A.
TRPC3
title_short Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus
title_full Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus
title_fullStr Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus
title_full_unstemmed Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus
title_sort Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus
dc.creator.none.fl_str_mv Cozart, Michael A.
Phelan, Kevin D.
Wu, Hong
Mu, Shengyu
Birnbaumer, Lutz
Rusch, Nancy J.
Zheng, Fang
author Cozart, Michael A.
author_facet Cozart, Michael A.
Phelan, Kevin D.
Wu, Hong
Mu, Shengyu
Birnbaumer, Lutz
Rusch, Nancy J.
Zheng, Fang
author_role author
author2 Phelan, Kevin D.
Wu, Hong
Mu, Shengyu
Birnbaumer, Lutz
Rusch, Nancy J.
Zheng, Fang
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv TRPC3
topic TRPC3
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Human status epilepticus (SE) is associated with a pathological reduction in cerebral blood flow termed the inverse hemodynamic response (IHR). Canonical transient receptor potential 3 (TRPC3) channels are integral to the propagation of seizures in SE, and vascular smooth muscle cell (VSMC) TRPC3 channels participate in vasoconstriction. Therefore, we hypothesize that cerebrovascular TRPC3 channels may contribute to seizure-induced IHR. To examine this possibility, we developed a smooth muscle-specific TRPC3 knockout (TRPC3smcKO) mouse. To quantify changes in neurovascular coupling, we combined laser speckle contrast imaging with simultaneous electroencephalogram recordings. Control mice exhibited multiple IHRs, and a limited increase in cerebral blood flow during SE with a high degree of moment-to-moment variability in which blood flow was not correlated with neuronal activity. In contrast, TRPC3smcKO mice showed a greater increase in blood flow that was less variable and was positively correlated with neuronal activity. Genetic ablation of smooth muscle TRPC3 channels shortened the duration of SE by eliminating a secondary phase of intense seizures, which was evident in littermate controls. Our results are consistent with the idea that TRPC3 channels expressed by cerebral VSMCs contribute to the IHR during SE, which is a critical factor in the progression of SE.
Fil: Cozart, Michael A.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Phelan, Kevin D.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Wu, Hong. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Mu, Shengyu. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Rusch, Nancy J.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Zheng, Fang. University of Arkansas for Medical Sciences; Estados Unidos
description Human status epilepticus (SE) is associated with a pathological reduction in cerebral blood flow termed the inverse hemodynamic response (IHR). Canonical transient receptor potential 3 (TRPC3) channels are integral to the propagation of seizures in SE, and vascular smooth muscle cell (VSMC) TRPC3 channels participate in vasoconstriction. Therefore, we hypothesize that cerebrovascular TRPC3 channels may contribute to seizure-induced IHR. To examine this possibility, we developed a smooth muscle-specific TRPC3 knockout (TRPC3smcKO) mouse. To quantify changes in neurovascular coupling, we combined laser speckle contrast imaging with simultaneous electroencephalogram recordings. Control mice exhibited multiple IHRs, and a limited increase in cerebral blood flow during SE with a high degree of moment-to-moment variability in which blood flow was not correlated with neuronal activity. In contrast, TRPC3smcKO mice showed a greater increase in blood flow that was less variable and was positively correlated with neuronal activity. Genetic ablation of smooth muscle TRPC3 channels shortened the duration of SE by eliminating a secondary phase of intense seizures, which was evident in littermate controls. Our results are consistent with the idea that TRPC3 channels expressed by cerebral VSMCs contribute to the IHR during SE, which is a critical factor in the progression of SE.
publishDate 2020
dc.date.none.fl_str_mv 2020-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/141701
Cozart, Michael A.; Phelan, Kevin D.; Wu, Hong; Mu, Shengyu; Birnbaumer, Lutz; et al.; Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus; Nature; Scientific Reports; 10; 1; 12-2020; 1-10
1476-4687
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/141701
identifier_str_mv Cozart, Michael A.; Phelan, Kevin D.; Wu, Hong; Mu, Shengyu; Birnbaumer, Lutz; et al.; Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus; Nature; Scientific Reports; 10; 1; 12-2020; 1-10
1476-4687
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-57733-0
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-020-57733-0
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature
publisher.none.fl_str_mv Nature
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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