Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis

Altered synaptic transmission with excess glutamate release has been implicated in the loss of motoneurons occurring in amyotrophic lateral sclerosis (ALS). Hyperexcitability or hypoexcitability of motoneurons from mice carrying the ALS mutation SOD1G93A (mSOD1) has also been reported. Here we have...

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Autores: Calvo-Gallardo, Enrique, de Pascual, Ricardo, Fernández Morales, José Carlos, Arranz-Tagarro, Juan Alberto, Maroto, Marcos, Pérez de Nanclares Fernández, Carmen, Gandía Juan, Luis, de Diego, Antonio M G, Padín, Juan Fernando, García García, Antonio
Tipo de documento: artigo
Data de publicação:2015
País:España
Recursos:Universidad Autónoma de Madrid
Repositório:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglês
OAI Identifier:oai:repositorio.uam.es:10486/672400
Acesso em linha:http://hdl.handle.net/10486/672400
https://dx.doi.org/10.1152/ajpcell.00272.2014
Access Level:Acceso aberto
Palavra-chave:Amyotrophic lateral sclerosis
Fusion pore
Chromaffin cells
Exocytosis
Ion channel currents
Medicina
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spelling Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosisCalvo-Gallardo, Enriquede Pascual, RicardoFernández Morales, José CarlosArranz-Tagarro, Juan AlbertoMaroto, MarcosPérez de Nanclares Fernández, CarmenGandía Juan, Luisde Diego, Antonio M GPadín, Juan FernandoGarcía García, AntonioAmyotrophic lateral sclerosisFusion poreChromaffin cellsExocytosisIon channel currentsMedicinaAltered synaptic transmission with excess glutamate release has been implicated in the loss of motoneurons occurring in amyotrophic lateral sclerosis (ALS). Hyperexcitability or hypoexcitability of motoneurons from mice carrying the ALS mutation SOD1G93A (mSOD1) has also been reported. Here we have investigated the excitability, the ion currents, and the kinetics of the exocytotic fusion pore in chromaffin cells from postnatal day 90 to postnatal day 130 mSOD1 mice, when motor deficits are already established. With respect to wild-type (WT), mSOD1 chromaffin cells had a decrease in the following parameters: 95% in spontaneous action potentials, 70% in nicotinic current for acetylcholine (ACh), 35% in Na+ current, 40% in Ca2+-dependent K+ current, and 53% in voltage-dependent K+ current. Ca2+ current was increased by 37%, but the ACh-evoked elevation of cytosolic Ca2+ was unchanged. Single exocytotic spike events triggered by ACh had the following differences (mSOD1 vs. WT): 36% lower rise rate, 60% higher decay time, 51% higher half-width, 13% lower amplitude, and 61% higher quantal size. The expression of the α3-subtype of nicotinic receptors and proteins of the exocytotic machinery was unchanged in the brain and adrenal medulla of mSOD1, with respect to WT mice. A slower fusion pore opening, expansion, and closure are likely linked to the pronounced reduction in cell excitability and in the ion currents driving action potentials in mSOD1, compared with WT chromaffin cells.This work was funded by: (1) SAF-2010-21795, MINECO; (2) SAF-2010-792 18837, MINECO; (3) CABICYC, UAM/Bioibérica; (4) Fundación Teófilo 793 Hernando, Madrid, SpainAmerican Physiological SocietyDepartamento de FarmacologíaFacultad de Medicina20152015-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/672400https://dx.doi.org/10.1152/ajpcell.00272.2014reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6724002026-06-23T12:46:27Z
dc.title.none.fl_str_mv Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis
title Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis
spellingShingle Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis
Calvo-Gallardo, Enrique
Amyotrophic lateral sclerosis
Fusion pore
Chromaffin cells
Exocytosis
Ion channel currents
Medicina
title_short Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis
title_full Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis
title_fullStr Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis
title_full_unstemmed Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis
title_sort Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis
dc.creator.none.fl_str_mv Calvo-Gallardo, Enrique
de Pascual, Ricardo
Fernández Morales, José Carlos
Arranz-Tagarro, Juan Alberto
Maroto, Marcos
Pérez de Nanclares Fernández, Carmen
Gandía Juan, Luis
de Diego, Antonio M G
Padín, Juan Fernando
García García, Antonio
author Calvo-Gallardo, Enrique
author_facet Calvo-Gallardo, Enrique
de Pascual, Ricardo
Fernández Morales, José Carlos
Arranz-Tagarro, Juan Alberto
Maroto, Marcos
Pérez de Nanclares Fernández, Carmen
Gandía Juan, Luis
de Diego, Antonio M G
Padín, Juan Fernando
García García, Antonio
author_role author
author2 de Pascual, Ricardo
Fernández Morales, José Carlos
Arranz-Tagarro, Juan Alberto
Maroto, Marcos
Pérez de Nanclares Fernández, Carmen
Gandía Juan, Luis
de Diego, Antonio M G
Padín, Juan Fernando
García García, Antonio
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Farmacología
Facultad de Medicina
dc.subject.none.fl_str_mv Amyotrophic lateral sclerosis
Fusion pore
Chromaffin cells
Exocytosis
Ion channel currents
Medicina
topic Amyotrophic lateral sclerosis
Fusion pore
Chromaffin cells
Exocytosis
Ion channel currents
Medicina
description Altered synaptic transmission with excess glutamate release has been implicated in the loss of motoneurons occurring in amyotrophic lateral sclerosis (ALS). Hyperexcitability or hypoexcitability of motoneurons from mice carrying the ALS mutation SOD1G93A (mSOD1) has also been reported. Here we have investigated the excitability, the ion currents, and the kinetics of the exocytotic fusion pore in chromaffin cells from postnatal day 90 to postnatal day 130 mSOD1 mice, when motor deficits are already established. With respect to wild-type (WT), mSOD1 chromaffin cells had a decrease in the following parameters: 95% in spontaneous action potentials, 70% in nicotinic current for acetylcholine (ACh), 35% in Na+ current, 40% in Ca2+-dependent K+ current, and 53% in voltage-dependent K+ current. Ca2+ current was increased by 37%, but the ACh-evoked elevation of cytosolic Ca2+ was unchanged. Single exocytotic spike events triggered by ACh had the following differences (mSOD1 vs. WT): 36% lower rise rate, 60% higher decay time, 51% higher half-width, 13% lower amplitude, and 61% higher quantal size. The expression of the α3-subtype of nicotinic receptors and proteins of the exocytotic machinery was unchanged in the brain and adrenal medulla of mSOD1, with respect to WT mice. A slower fusion pore opening, expansion, and closure are likely linked to the pronounced reduction in cell excitability and in the ion currents driving action potentials in mSOD1, compared with WT chromaffin cells.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-01-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/672400
https://dx.doi.org/10.1152/ajpcell.00272.2014
url http://hdl.handle.net/10486/672400
https://dx.doi.org/10.1152/ajpcell.00272.2014
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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