TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons

Autores
Um, Ki Bum; Hahn, Suyun; Kim, So Woon; Lee, Yoon Je; Birnbaumer, Lutz; Kim, Hyun Jin; Park, Myoung Kyu
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fil: Um, Ki Bum. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Hahn, Suyun. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Kim, So Woon. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Lee, Yoon Je. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Kim, Hyun Jin. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Kim, Hyun Jin. Centro Médico Samsung. Instituto de Investigación Biomédica de Samsung; República de Corea
Fil: Park, Myoung Kyu. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Park, Myoung Kyu. Centro Médico Samsung. Instituto de Investigación Biomédica de Samsung; República de Corea
Abstract: Midbrain dopamine (DA) neurons are slow pacemakers that maintain extracellular DA levels. During the interspike intervals, subthreshold slow depolarization underlies autonomous pacemaking and determines its rate. However, the ion channels that determine slow depolarization are unknown. Here we show that TRPC3 and NALCN channels together form sustained inward currents responsible for the slow depolarization of nigral DA neurons. Specific TRPC3 channel blockade completely blocked DA neuron pacemaking, but the pacemaking activity in TRPC3 knock-out (KO) mice was perfectly normal, suggesting the presence of compensating ion channels. Blocking NALCN channels abolished pacemaking in both TRPC3 KO and wild-type mice. The NALCN current and mRNA and protein expression are increased in TRPC3 KO mice, indicating that NALCN compensates for TRPC3 currents. In normal conditions, TRPC3 and NALCN contribute equally to slow depolarization. Therefore, we conclude that TRPC3 and NALCN are two major leak channels that drive robust pacemaking in nigral DA neurons.
Fuente
eLife. 2021
Materia
TRPC3
NALCN
NEURONAS
DOPAMINA
SISTEMA NERVIOSO CENTRAL
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/13952
Acceder
id RIUCA_1df1e24409d9d8ea0ee86d1fbe20e5d5
oai_identifier_str oai:ucacris:123456789/13952
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
spelling TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neuronsUm, Ki BumHahn, SuyunKim, So WoonLee, Yoon JeBirnbaumer, LutzKim, Hyun JinPark, Myoung KyuTRPC3NALCNNEURONASDOPAMINASISTEMA NERVIOSO CENTRALFil: Um, Ki Bum. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de CoreaFil: Hahn, Suyun. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de CoreaFil: Kim, So Woon. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de CoreaFil: Lee, Yoon Je. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de CoreaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Kim, Hyun Jin. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de CoreaFil: Kim, Hyun Jin. Centro Médico Samsung. Instituto de Investigación Biomédica de Samsung; República de CoreaFil: Park, Myoung Kyu. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de CoreaFil: Park, Myoung Kyu. Centro Médico Samsung. Instituto de Investigación Biomédica de Samsung; República de CoreaAbstract: Midbrain dopamine (DA) neurons are slow pacemakers that maintain extracellular DA levels. During the interspike intervals, subthreshold slow depolarization underlies autonomous pacemaking and determines its rate. However, the ion channels that determine slow depolarization are unknown. Here we show that TRPC3 and NALCN channels together form sustained inward currents responsible for the slow depolarization of nigral DA neurons. Specific TRPC3 channel blockade completely blocked DA neuron pacemaking, but the pacemaking activity in TRPC3 knock-out (KO) mice was perfectly normal, suggesting the presence of compensating ion channels. Blocking NALCN channels abolished pacemaking in both TRPC3 KO and wild-type mice. The NALCN current and mRNA and protein expression are increased in TRPC3 KO mice, indicating that NALCN compensates for TRPC3 currents. In normal conditions, TRPC3 and NALCN contribute equally to slow depolarization. Therefore, we conclude that TRPC3 and NALCN are two major leak channels that drive robust pacemaking in nigral DA neurons.eLife0000-0002-4882-57362021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/1395210.7554/eLife.7092034409942Um, K. B. et al. TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons [en línea]. eLife. 2021. doi: 10.7554/eLife.70920. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/13952eLife. 2021reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:58:33Zoai:ucacris:123456789/13952instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:58:33.781Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse
dc.title.none.fl_str_mv TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
title TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
spellingShingle TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
Um, Ki Bum
TRPC3
NALCN
NEURONAS
DOPAMINA
SISTEMA NERVIOSO CENTRAL
title_short TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
title_full TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
title_fullStr TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
title_full_unstemmed TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
title_sort TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
dc.creator.none.fl_str_mv Um, Ki Bum
Hahn, Suyun
Kim, So Woon
Lee, Yoon Je
Birnbaumer, Lutz
Kim, Hyun Jin
Park, Myoung Kyu
author Um, Ki Bum
author_facet Um, Ki Bum
Hahn, Suyun
Kim, So Woon
Lee, Yoon Je
Birnbaumer, Lutz
Kim, Hyun Jin
Park, Myoung Kyu
author_role author
author2 Hahn, Suyun
Kim, So Woon
Lee, Yoon Je
Birnbaumer, Lutz
Kim, Hyun Jin
Park, Myoung Kyu
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv 0000-0002-4882-5736
dc.subject.none.fl_str_mv TRPC3
NALCN
NEURONAS
DOPAMINA
SISTEMA NERVIOSO CENTRAL
topic TRPC3
NALCN
NEURONAS
DOPAMINA
SISTEMA NERVIOSO CENTRAL
dc.description.none.fl_txt_mv Fil: Um, Ki Bum. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Hahn, Suyun. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Kim, So Woon. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Lee, Yoon Je. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Kim, Hyun Jin. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Kim, Hyun Jin. Centro Médico Samsung. Instituto de Investigación Biomédica de Samsung; República de Corea
Fil: Park, Myoung Kyu. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
Fil: Park, Myoung Kyu. Centro Médico Samsung. Instituto de Investigación Biomédica de Samsung; República de Corea
Abstract: Midbrain dopamine (DA) neurons are slow pacemakers that maintain extracellular DA levels. During the interspike intervals, subthreshold slow depolarization underlies autonomous pacemaking and determines its rate. However, the ion channels that determine slow depolarization are unknown. Here we show that TRPC3 and NALCN channels together form sustained inward currents responsible for the slow depolarization of nigral DA neurons. Specific TRPC3 channel blockade completely blocked DA neuron pacemaking, but the pacemaking activity in TRPC3 knock-out (KO) mice was perfectly normal, suggesting the presence of compensating ion channels. Blocking NALCN channels abolished pacemaking in both TRPC3 KO and wild-type mice. The NALCN current and mRNA and protein expression are increased in TRPC3 KO mice, indicating that NALCN compensates for TRPC3 currents. In normal conditions, TRPC3 and NALCN contribute equally to slow depolarization. Therefore, we conclude that TRPC3 and NALCN are two major leak channels that drive robust pacemaking in nigral DA neurons.
description Fil: Um, Ki Bum. Universidad Sungkyunkwan. Facultad de Medicina. Departamento de fisiología; República de Corea
publishDate 2021
dc.date.none.fl_str_mv 2021
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 https://repositorio.uca.edu.ar/handle/123456789/13952
10.7554/eLife.70920
34409942
Um, K. B. et al. TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons [en línea]. eLife. 2021. doi: 10.7554/eLife.70920. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/13952
url https://repositorio.uca.edu.ar/handle/123456789/13952
identifier_str_mv 10.7554/eLife.70920
34409942
Um, K. B. et al. TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons [en línea]. eLife. 2021. doi: 10.7554/eLife.70920. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/13952
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv eLife
publisher.none.fl_str_mv eLife
dc.source.none.fl_str_mv eLife. 2021
reponame:Repositorio Institucional (UCA)
instname:Pontificia Universidad Católica Argentina
reponame_str Repositorio Institucional (UCA)
collection Repositorio Institucional (UCA)
instname_str Pontificia Universidad Católica Argentina
repository.name.fl_str_mv Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina
repository.mail.fl_str_mv claudia_fernandez@uca.edu.ar
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score 13.13397

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