Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism

Autores
Tubert, Cecilia; Taravini, Irene Rita Eloisa; Flores Barrera, Eden; Sanchez, Gonzalo Manuel; Prost, María Alejandra; Avale, Maria Elena; Tseng, Kuei Y.; Rela, Lorena; Murer, Mario Gustavo
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The mechanism underlying a hypercholinergic state in Parkinson’s disease (PD) remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by Kv1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on KCa channels.
Fil: Tubert, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Taravini, Irene Rita Eloisa. Universidad Nacional de Entre Ríos. Facultad de Bromatología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Flores Barrera, Eden. Rosalind Franklin University Of Medicine & Science. The Chicago Medical School. Department Of Cellular & Molecular Pharmacology; Estados Unidos
Fil: Sanchez, Gonzalo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Prost, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Avale, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina
Fil: Tseng, Kuei Y.. Rosalind Franklin University Of Medicine & Science. The Chicago Medical School. Department Of Cellular & Molecular Pharmacology; Estados Unidos
Fil: Rela, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Materia
Parkinson´S Disease
Striatal Cholinergic Interneurons
Excitability
Kv1.3
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/45146
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental ParkinsonismTubert, CeciliaTaravini, Irene Rita EloisaFlores Barrera, EdenSanchez, Gonzalo ManuelProst, María AlejandraAvale, Maria ElenaTseng, Kuei Y.Rela, LorenaMurer, Mario GustavoParkinson´S DiseaseStriatal Cholinergic InterneuronsExcitabilityKv1.3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The mechanism underlying a hypercholinergic state in Parkinson’s disease (PD) remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by Kv1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on KCa channels.Fil: Tubert, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Taravini, Irene Rita Eloisa. Universidad Nacional de Entre Ríos. Facultad de Bromatología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Flores Barrera, Eden. Rosalind Franklin University Of Medicine & Science. The Chicago Medical School. Department Of Cellular & Molecular Pharmacology; Estados UnidosFil: Sanchez, Gonzalo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Prost, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Avale, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; ArgentinaFil: Tseng, Kuei Y.. Rosalind Franklin University Of Medicine & Science. The Chicago Medical School. Department Of Cellular & Molecular Pharmacology; Estados UnidosFil: Rela, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaElsevier2016-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/45146Tubert, Cecilia; Taravini, Irene Rita Eloisa; Flores Barrera, Eden; Sanchez, Gonzalo Manuel; Prost, María Alejandra; et al.; Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism; Elsevier; Cell Reports; 16; 10; 9-2016; 2749-27622211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S2211124716310622info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2016.08.016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:28Zoai:ri.conicet.gov.ar:11336/45146instacron: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 09:56:28.342CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism
title Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism
spellingShingle Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism
Tubert, Cecilia
Parkinson´S Disease
Striatal Cholinergic Interneurons
Excitability
Kv1.3
title_short Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism
title_full Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism
title_fullStr Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism
title_full_unstemmed Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism
title_sort Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism
dc.creator.none.fl_str_mv Tubert, Cecilia
Taravini, Irene Rita Eloisa
Flores Barrera, Eden
Sanchez, Gonzalo Manuel
Prost, María Alejandra
Avale, Maria Elena
Tseng, Kuei Y.
Rela, Lorena
Murer, Mario Gustavo
author Tubert, Cecilia
author_facet Tubert, Cecilia
Taravini, Irene Rita Eloisa
Flores Barrera, Eden
Sanchez, Gonzalo Manuel
Prost, María Alejandra
Avale, Maria Elena
Tseng, Kuei Y.
Rela, Lorena
Murer, Mario Gustavo
author_role author
author2 Taravini, Irene Rita Eloisa
Flores Barrera, Eden
Sanchez, Gonzalo Manuel
Prost, María Alejandra
Avale, Maria Elena
Tseng, Kuei Y.
Rela, Lorena
Murer, Mario Gustavo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Parkinson´S Disease
Striatal Cholinergic Interneurons
Excitability
Kv1.3
topic Parkinson´S Disease
Striatal Cholinergic Interneurons
Excitability
Kv1.3
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The mechanism underlying a hypercholinergic state in Parkinson’s disease (PD) remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by Kv1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on KCa channels.
Fil: Tubert, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Taravini, Irene Rita Eloisa. Universidad Nacional de Entre Ríos. Facultad de Bromatología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Flores Barrera, Eden. Rosalind Franklin University Of Medicine & Science. The Chicago Medical School. Department Of Cellular & Molecular Pharmacology; Estados Unidos
Fil: Sanchez, Gonzalo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Prost, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Avale, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina
Fil: Tseng, Kuei Y.. Rosalind Franklin University Of Medicine & Science. The Chicago Medical School. Department Of Cellular & Molecular Pharmacology; Estados Unidos
Fil: Rela, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
description The mechanism underlying a hypercholinergic state in Parkinson’s disease (PD) remains uncertain. Here, we show that disruption of the Kv1 channel-mediated function causes hyperexcitability of striatal cholinergic interneurons in a mouse model of PD. Specifically, our data reveal that Kv1 channels containing Kv1.3 subunits contribute significantly to the orphan potassium current known as IsAHP in striatal cholinergic interneurons. Typically, this Kv1 current provides negative feedback to depolarization that limits burst firing and slows the tonic activity of cholinergic interneurons. However, such inhibitory control of cholinergic interneuron excitability by Kv1.3-mediated current is markedly diminished in the parkinsonian striatum, suggesting that targeting Kv1.3 subunits and their regulatory pathways may have therapeutic potential in PD therapy. These studies reveal unexpected roles of Kv1.3 subunit-containing channels in the regulation of firing patterns of striatal cholinergic interneurons, which were thought to be largely dependent on KCa channels.
publishDate 2016
dc.date.none.fl_str_mv 2016-09
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/11336/45146
Tubert, Cecilia; Taravini, Irene Rita Eloisa; Flores Barrera, Eden; Sanchez, Gonzalo Manuel; Prost, María Alejandra; et al.; Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism; Elsevier; Cell Reports; 16; 10; 9-2016; 2749-2762
2211-1247
CONICET Digital
CONICET
url http://hdl.handle.net/11336/45146
identifier_str_mv Tubert, Cecilia; Taravini, Irene Rita Eloisa; Flores Barrera, Eden; Sanchez, Gonzalo Manuel; Prost, María Alejandra; et al.; Decrease of a Current Mediated by K v 1.3 Channels Causes Striatal Cholinergic Interneuron Hyperexcitability in Experimental Parkinsonism; Elsevier; Cell Reports; 16; 10; 9-2016; 2749-2762
2211-1247
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S2211124716310622
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2016.08.016
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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