TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice

Autores
Phelan, Kevin D.; Shwe, U Thaung; Cozart, Michael A.; Wu, Hong; Mock, Matthew M.; Abramowitz, Joel; Birnbaumer, Lutz; Zheng, Fang
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced status epilepticus (SE). Methods: The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine-induced seizures were performed. Results: We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity, which dominates both the preictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Significance: Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs.
Fil: Phelan, Kevin D.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Shwe, U Thaung. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Cozart, Michael A.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Wu, Hong. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Mock, Matthew M.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Abramowitz, Joel. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences; Estados Unidos. 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: Zheng, Fang. University of Arkansas for Medical Sciences; Estados Unidos
Materia
Beta Rhythm
Electroencephalography
Gamma Rhythm
Seizures
Spectral Analysis
Transient Receptor Potential Channels
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/47700
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/47700
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in micePhelan, Kevin D.Shwe, U ThaungCozart, Michael A.Wu, HongMock, Matthew M.Abramowitz, JoelBirnbaumer, LutzZheng, FangBeta RhythmElectroencephalographyGamma RhythmSeizuresSpectral AnalysisTransient Receptor Potential Channelshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Objective: Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced status epilepticus (SE). Methods: The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine-induced seizures were performed. Results: We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity, which dominates both the preictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Significance: Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs.Fil: Phelan, Kevin D.. University of Arkansas for Medical Sciences; Estados UnidosFil: Shwe, U Thaung. University of Arkansas for Medical Sciences; Estados UnidosFil: Cozart, Michael A.. University of Arkansas for Medical Sciences; Estados UnidosFil: Wu, Hong. University of Arkansas for Medical Sciences; Estados UnidosFil: Mock, Matthew M.. University of Arkansas for Medical Sciences; Estados UnidosFil: Abramowitz, Joel. National Institute of Environmental Health Sciences; Estados UnidosFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences; Estados Unidos. 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: Zheng, Fang. University of Arkansas for Medical Sciences; Estados UnidosWiley Blackwell Publishing, Inc2017-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47700Phelan, Kevin D.; Shwe, U Thaung; Cozart, Michael A.; Wu, Hong; Mock, Matthew M.; et al.; TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice; Wiley Blackwell Publishing, Inc; Epilepsia; 58; 2; 2-2017; 247-2540013-9580CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/epi.13648info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.13648info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-03T08:49:17Zoai:ri.conicet.gov.ar:11336/47700instacron: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:34982025-12-03 08:49:17.53CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice
title TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice
spellingShingle TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice
Phelan, Kevin D.
Beta Rhythm
Electroencephalography
Gamma Rhythm
Seizures
Spectral Analysis
Transient Receptor Potential Channels
title_short TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice
title_full TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice
title_fullStr TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice
title_full_unstemmed TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice
title_sort TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice
dc.creator.none.fl_str_mv Phelan, Kevin D.
Shwe, U Thaung
Cozart, Michael A.
Wu, Hong
Mock, Matthew M.
Abramowitz, Joel
Birnbaumer, Lutz
Zheng, Fang
author Phelan, Kevin D.
author_facet Phelan, Kevin D.
Shwe, U Thaung
Cozart, Michael A.
Wu, Hong
Mock, Matthew M.
Abramowitz, Joel
Birnbaumer, Lutz
Zheng, Fang
author_role author
author2 Shwe, U Thaung
Cozart, Michael A.
Wu, Hong
Mock, Matthew M.
Abramowitz, Joel
Birnbaumer, Lutz
Zheng, Fang
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Beta Rhythm
Electroencephalography
Gamma Rhythm
Seizures
Spectral Analysis
Transient Receptor Potential Channels
topic Beta Rhythm
Electroencephalography
Gamma Rhythm
Seizures
Spectral Analysis
Transient Receptor Potential Channels
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective: Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced status epilepticus (SE). Methods: The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine-induced seizures were performed. Results: We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity, which dominates both the preictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Significance: Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs.
Fil: Phelan, Kevin D.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Shwe, U Thaung. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Cozart, Michael A.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Wu, Hong. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Mock, Matthew M.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Abramowitz, Joel. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences; Estados Unidos. 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: Zheng, Fang. University of Arkansas for Medical Sciences; Estados Unidos
description Objective: Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced status epilepticus (SE). Methods: The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine-induced seizures were performed. Results: We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity, which dominates both the preictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Significance: Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs.
publishDate 2017
dc.date.none.fl_str_mv 2017-02
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/11336/47700
Phelan, Kevin D.; Shwe, U Thaung; Cozart, Michael A.; Wu, Hong; Mock, Matthew M.; et al.; TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice; Wiley Blackwell Publishing, Inc; Epilepsia; 58; 2; 2-2017; 247-254
0013-9580
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47700
identifier_str_mv Phelan, Kevin D.; Shwe, U Thaung; Cozart, Michael A.; Wu, Hong; Mock, Matthew M.; et al.; TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice; Wiley Blackwell Publishing, Inc; Epilepsia; 58; 2; 2-2017; 247-254
0013-9580
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/epi.13648
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.13648
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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 13.214268

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