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

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dc.contributor.author Calvo-Gallardo, Enrique
dc.contributor.author de Pascual, Ricardo
dc.contributor.author Fernández Morales, José Carlos
dc.contributor.author Arranz-Tagarro, Juan Alberto
dc.contributor.author Maroto, Marcos
dc.contributor.author Nanclares, Carmen
dc.contributor.author Gandía, Luis
dc.contributor.author de Diego, Antonio M G
dc.contributor.author Padín, Juan Fernando
dc.contributor.author García, Antonio G.
dc.contributor.other UAM. Departamento de Farmacología es_ES
dc.date.accessioned 2016-08-09T13:29:57Z
dc.date.available 2016-08-09T13:29:57Z
dc.date.issued 2015-01-01
dc.identifier.citation American journal of physiology. Cell physiology 308.1 (2015): C1-C19 es_ES
dc.identifier.issn 0363-6143 (print) es_ES
dc.identifier.issn 1522-1563 (on line) es_ES
dc.identifier.uri http://hdl.handle.net/10486/672400
dc.description.abstract 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. es_ES
dc.description.sponsorship 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, Spain es_ES
dc.format.mimetype application/pdf es_ES
dc.language.iso eng es_ES
dc.publisher American Physiological Society es_ES
dc.relation.ispartof American journal of physiology. Cell physiology es_ES
dc.subject.other Amyotrophic lateral sclerosis es_ES
dc.subject.other Fusion pore es_ES
dc.subject.other Chromaffin cells es_ES
dc.subject.other Exocytosis es_ES
dc.subject.other Ion channel currents es_ES
dc.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 es_ES
dc.type article es_ES
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion http://dx.doi.org/10.1152/ajpcell.00272.2014 es_ES
dc.identifier.doi 10.1152/ajpcell.00272.2014 es_ES
dc.identifier.publicationfirstpage C1 es_ES
dc.identifier.publicationissue 1 es_ES
dc.identifier.publicationlastpage C19 es_ES
dc.identifier.publicationvolume 308 es_ES
dc.relation.projectID Gobierno de España. SAF-2010-21795 es_ES
dc.relation.projectID Gobierno de España. SAF-2010-792 18837, es_ES
dc.type.version info:eu-repo/semantics/acceptedVersion es_ES
dc.rights.accessRights openAccess es_ES
dc.authorUAM Fernández Morales, José Carlos (263594)


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