Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons

Autores
Benitez, Bruno A.; Belálcazar, Helen M.; Anastasia Gonzalez, Agustin; Mamah, Daniel; Zorumski, Charles; Masco, Daniel Hugo; Herrera, Daniel; de Erausquin, Gabriel Alejandro
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In primary cultures of mesencephalon small-conductance calcium-activated potassium channels (SK) are expressed in dopaminergic neurons. We characterized SK-mediated currents (ISK) in this system and evaluated their role on homeostasis against excitotoxicity. ISK amplitude was reduced by the glutamatergic agonist AMPA through a reduction in SK channel number in the membrane. Blockade of ISK for 12 h with apamin or NS8593 reduced the number of dopaminergic neurons in a concentration-dependent manner. The effect of apamin was not additive to AMPA toxicity. On the other hand, two ISK agonists,
1-EBIO and CyPPA, caused a significant reduction of spontaneous loss of dopaminergic neurons. 1-EBIO reversed the effects of both AMPA and apamin as well. Thus, ISK influences survival and differentiation of dopaminergic neurons in vitro, and is part of protective homeostatic responses, participating in a rapidly acting negative feedback loop coupling calcium levels, neuron excitability and cellular defenses. 
Fil: Benitez, Bruno A.. Harvard Medical School; Estados Unidos
Fil: Belálcazar, Helen M.. Harvard Medical School; Estados Unidos
Fil: Anastasia Gonzalez, Agustin. Washington University in St. Louis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Mamah, Daniel. Washington University in St. Louis; Estados Unidos
Fil: Zorumski, Charles. Washington University in St. Louis; Estados Unidos
Fil: Masco, Daniel Hugo. Washington University in St. Louis; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Herrera, Daniel. Harvard Medical School; Estados Unidos
Fil: de Erausquin, Gabriel Alejandro. Harvard Medical School; Estados Unidos
Materia
Dopaminergic Neurons
Sk3 Channels
Protection
Calcium
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:11336/42889
Acceder
id CONICETDig_62875a52d88009cb5cd48f25afda82b2
oai_identifier_str oai:ri.conicet.gov.ar:11336/42889
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neuronsBenitez, Bruno A.Belálcazar, Helen M.Anastasia Gonzalez, AgustinMamah, DanielZorumski, CharlesMasco, Daniel HugoHerrera, Danielde Erausquin, Gabriel AlejandroDopaminergic NeuronsSk3 ChannelsProtectionCalciumhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In primary cultures of mesencephalon small-conductance calcium-activated potassium channels (SK) are expressed in dopaminergic neurons. We characterized SK-mediated currents (ISK) in this system and evaluated their role on homeostasis against excitotoxicity. ISK amplitude was reduced by the glutamatergic agonist AMPA through a reduction in SK channel number in the membrane. Blockade of ISK for 12 h with apamin or NS8593 reduced the number of dopaminergic neurons in a concentration-dependent manner. The effect of apamin was not additive to AMPA toxicity. On the other hand, two ISK agonists,<br />1-EBIO and CyPPA, caused a significant reduction of spontaneous loss of dopaminergic neurons. 1-EBIO reversed the effects of both AMPA and apamin as well. Thus, ISK influences survival and differentiation of dopaminergic neurons in vitro, and is part of protective homeostatic responses, participating in a rapidly acting negative feedback loop coupling calcium levels, neuron excitability and cellular defenses. Fil: Benitez, Bruno A.. Harvard Medical School; Estados UnidosFil: Belálcazar, Helen M.. Harvard Medical School; Estados UnidosFil: Anastasia Gonzalez, Agustin. Washington University in St. Louis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Mamah, Daniel. Washington University in St. Louis; Estados UnidosFil: Zorumski, Charles. Washington University in St. Louis; Estados UnidosFil: Masco, Daniel Hugo. Washington University in St. Louis; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Herrera, Daniel. Harvard Medical School; Estados UnidosFil: de Erausquin, Gabriel Alejandro. Harvard Medical School; Estados UnidosPergamon-Elsevier Science Ltd2011-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/42889Benitez, Bruno A.; Belálcazar, Helen M.; Anastasia Gonzalez, Agustin; Mamah, Daniel; Zorumski, Charles; et al.; Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons; Pergamon-Elsevier Science Ltd; Neuropharmacology; 60; 7-8; 6-2011; 1176-11860028-3908CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0028390810002947info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuropharm.2010.10.024info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:26Zoai:ri.conicet.gov.ar:11336/42889instacron: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 10:01:26.376CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons
title Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons
spellingShingle Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons
Benitez, Bruno A.
Dopaminergic Neurons
Sk3 Channels
Protection
Calcium
title_short Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons
title_full Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons
title_fullStr Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons
title_full_unstemmed Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons
title_sort Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons
dc.creator.none.fl_str_mv Benitez, Bruno A.
Belálcazar, Helen M.
Anastasia Gonzalez, Agustin
Mamah, Daniel
Zorumski, Charles
Masco, Daniel Hugo
Herrera, Daniel
de Erausquin, Gabriel Alejandro
author Benitez, Bruno A.
author_facet Benitez, Bruno A.
Belálcazar, Helen M.
Anastasia Gonzalez, Agustin
Mamah, Daniel
Zorumski, Charles
Masco, Daniel Hugo
Herrera, Daniel
de Erausquin, Gabriel Alejandro
author_role author
author2 Belálcazar, Helen M.
Anastasia Gonzalez, Agustin
Mamah, Daniel
Zorumski, Charles
Masco, Daniel Hugo
Herrera, Daniel
de Erausquin, Gabriel Alejandro
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Dopaminergic Neurons
Sk3 Channels
Protection
Calcium
topic Dopaminergic Neurons
Sk3 Channels
Protection
Calcium
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In primary cultures of mesencephalon small-conductance calcium-activated potassium channels (SK) are expressed in dopaminergic neurons. We characterized SK-mediated currents (ISK) in this system and evaluated their role on homeostasis against excitotoxicity. ISK amplitude was reduced by the glutamatergic agonist AMPA through a reduction in SK channel number in the membrane. Blockade of ISK for 12 h with apamin or NS8593 reduced the number of dopaminergic neurons in a concentration-dependent manner. The effect of apamin was not additive to AMPA toxicity. On the other hand, two ISK agonists,<br />1-EBIO and CyPPA, caused a significant reduction of spontaneous loss of dopaminergic neurons. 1-EBIO reversed the effects of both AMPA and apamin as well. Thus, ISK influences survival and differentiation of dopaminergic neurons in vitro, and is part of protective homeostatic responses, participating in a rapidly acting negative feedback loop coupling calcium levels, neuron excitability and cellular defenses. 
Fil: Benitez, Bruno A.. Harvard Medical School; Estados Unidos
Fil: Belálcazar, Helen M.. Harvard Medical School; Estados Unidos
Fil: Anastasia Gonzalez, Agustin. Washington University in St. Louis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Mamah, Daniel. Washington University in St. Louis; Estados Unidos
Fil: Zorumski, Charles. Washington University in St. Louis; Estados Unidos
Fil: Masco, Daniel Hugo. Washington University in St. Louis; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Herrera, Daniel. Harvard Medical School; Estados Unidos
Fil: de Erausquin, Gabriel Alejandro. Harvard Medical School; Estados Unidos
description In primary cultures of mesencephalon small-conductance calcium-activated potassium channels (SK) are expressed in dopaminergic neurons. We characterized SK-mediated currents (ISK) in this system and evaluated their role on homeostasis against excitotoxicity. ISK amplitude was reduced by the glutamatergic agonist AMPA through a reduction in SK channel number in the membrane. Blockade of ISK for 12 h with apamin or NS8593 reduced the number of dopaminergic neurons in a concentration-dependent manner. The effect of apamin was not additive to AMPA toxicity. On the other hand, two ISK agonists,<br />1-EBIO and CyPPA, caused a significant reduction of spontaneous loss of dopaminergic neurons. 1-EBIO reversed the effects of both AMPA and apamin as well. Thus, ISK influences survival and differentiation of dopaminergic neurons in vitro, and is part of protective homeostatic responses, participating in a rapidly acting negative feedback loop coupling calcium levels, neuron excitability and cellular defenses. 
publishDate 2011
dc.date.none.fl_str_mv 2011-06
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/11336/42889
Benitez, Bruno A.; Belálcazar, Helen M.; Anastasia Gonzalez, Agustin; Mamah, Daniel; Zorumski, Charles; et al.; Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons; Pergamon-Elsevier Science Ltd; Neuropharmacology; 60; 7-8; 6-2011; 1176-1186
0028-3908
CONICET Digital
CONICET
url http://hdl.handle.net/11336/42889
identifier_str_mv Benitez, Bruno A.; Belálcazar, Helen M.; Anastasia Gonzalez, Agustin; Mamah, Daniel; Zorumski, Charles; et al.; Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons; Pergamon-Elsevier Science Ltd; Neuropharmacology; 60; 7-8; 6-2011; 1176-1186
0028-3908
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/S0028390810002947
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuropharm.2010.10.024
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
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
_version_ 1842269693901012992
score 13.13397

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