Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held

Autores
González Inchauspe, Carlota María Fabiola; Urbano Suarez, Francisco Jose; Di Guilmi, Mariano Nicolás; Ferrari, Michel D.; Van den Maagdenberg, Arn M. J. M.; Forsythe, Ian; Uchitel, Osvaldo Daniel
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
CaV2.1 Ca2+ channels have a dominant and specific role in initiating fast synaptic transmission at central excitatory synapses, through a close association between release sites and calcium sensors. Familial hemiplegic migraine type-1 (FHM-1) is an autosomal-dominant subtype of migraine with aura, caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 channel. We used knock-in (KI) transgenic mice harbouring the FHM-1 mutation R192Q to study the consequences of this mutation in neurotransmission at the giant synapse of the auditory system formed by the presynaptic calyx of Held terminal and the postsynaptic neurons of the Medial Nucleus of the Trapezoid Body (MNTB). Although synaptic transmission seems unaffected by low frequency stimulation in physiological Ca2+ concentration, we observed that with low Ca2+concentrations (< 1 mM) excitatory postsynaptic currents (EPSCs) showed increased amplitudes in R192Q KI mice compared to WT, meaning significant differences in the non-linear calcium-dependence of nerve-evoked transmitter release. In addition, when EPSCs were evoked by broadened presynaptic action potentials (achieved by inhibition of K+channels) via Cav2.1 triggered exocytosis, the R192Q KI mice exhibited further enhancement of EPSC amplitude and charge compared with WT mice. Repetitive stimulation of afferent axons to the MNTB at different frequencies caused short term depression of EPSCs that recovered significantly faster in R192Q KI than in WT mice. Faster recovery in R192Q KI mice was prevented by the calcium chelator EGTA-AM, pointing to enlarged residual calcium as a key factor in accelerating the replenishment of synaptic vesicles.
Fil: González Inchauspe, Carlota María Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Di Guilmi, Mariano Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Ferrari, Michel D.. Leiden University Medical Centre; Países Bajos
Fil: Van den Maagdenberg, Arn M. J. M.. Leiden University Medical Centre; Países Bajos
Fil: Forsythe, Ian. University of Leicester; Reino Unido
Fil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Materia
R192Q KI MICE
FAMILIAL HEMIPLEGIC MIGRAINE
CAV2.1 CALCIUM CHANNELS
EXCITATORY POSTSYNAPTIC CURRENTS
SHORT TERM SYNAPTIC PLASTICITY
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:11336/85639
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/85639
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of heldGonzález Inchauspe, Carlota María FabiolaUrbano Suarez, Francisco JoseDi Guilmi, Mariano NicolásFerrari, Michel D.Van den Maagdenberg, Arn M. J. M.Forsythe, IanUchitel, Osvaldo DanielR192Q KI MICEFAMILIAL HEMIPLEGIC MIGRAINECAV2.1 CALCIUM CHANNELSEXCITATORY POSTSYNAPTIC CURRENTSSHORT TERM SYNAPTIC PLASTICITYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3CaV2.1 Ca2+ channels have a dominant and specific role in initiating fast synaptic transmission at central excitatory synapses, through a close association between release sites and calcium sensors. Familial hemiplegic migraine type-1 (FHM-1) is an autosomal-dominant subtype of migraine with aura, caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 channel. We used knock-in (KI) transgenic mice harbouring the FHM-1 mutation R192Q to study the consequences of this mutation in neurotransmission at the giant synapse of the auditory system formed by the presynaptic calyx of Held terminal and the postsynaptic neurons of the Medial Nucleus of the Trapezoid Body (MNTB). Although synaptic transmission seems unaffected by low frequency stimulation in physiological Ca2+ concentration, we observed that with low Ca2+concentrations (< 1 mM) excitatory postsynaptic currents (EPSCs) showed increased amplitudes in R192Q KI mice compared to WT, meaning significant differences in the non-linear calcium-dependence of nerve-evoked transmitter release. In addition, when EPSCs were evoked by broadened presynaptic action potentials (achieved by inhibition of K+channels) via Cav2.1 triggered exocytosis, the R192Q KI mice exhibited further enhancement of EPSC amplitude and charge compared with WT mice. Repetitive stimulation of afferent axons to the MNTB at different frequencies caused short term depression of EPSCs that recovered significantly faster in R192Q KI than in WT mice. Faster recovery in R192Q KI mice was prevented by the calcium chelator EGTA-AM, pointing to enlarged residual calcium as a key factor in accelerating the replenishment of synaptic vesicles.Fil: González Inchauspe, Carlota María Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Di Guilmi, Mariano Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Ferrari, Michel D.. Leiden University Medical Centre; Países BajosFil: Van den Maagdenberg, Arn M. J. M.. Leiden University Medical Centre; Países BajosFil: Forsythe, Ian. University of Leicester; Reino UnidoFil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaAmerican Physiological Society2012-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/85639González Inchauspe, Carlota María Fabiola; Urbano Suarez, Francisco Jose; Di Guilmi, Mariano Nicolás; Ferrari, Michel D.; Van den Maagdenberg, Arn M. J. M.; et al.; Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held; American Physiological Society; Journal of Neurophysiology; 108; 11; 12-2012; 2967-29760022-3077CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/ 10.1152/jn.01183.2011info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/jn.01183.2011info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:54:06Zoai:ri.conicet.gov.ar:11336/85639instacron: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:34982025-10-22 11:54:06.697CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held
title Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held
spellingShingle Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held
González Inchauspe, Carlota María Fabiola
R192Q KI MICE
FAMILIAL HEMIPLEGIC MIGRAINE
CAV2.1 CALCIUM CHANNELS
EXCITATORY POSTSYNAPTIC CURRENTS
SHORT TERM SYNAPTIC PLASTICITY
title_short Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held
title_full Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held
title_fullStr Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held
title_full_unstemmed Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held
title_sort Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held
dc.creator.none.fl_str_mv González Inchauspe, Carlota María Fabiola
Urbano Suarez, Francisco Jose
Di Guilmi, Mariano Nicolás
Ferrari, Michel D.
Van den Maagdenberg, Arn M. J. M.
Forsythe, Ian
Uchitel, Osvaldo Daniel
author González Inchauspe, Carlota María Fabiola
author_facet González Inchauspe, Carlota María Fabiola
Urbano Suarez, Francisco Jose
Di Guilmi, Mariano Nicolás
Ferrari, Michel D.
Van den Maagdenberg, Arn M. J. M.
Forsythe, Ian
Uchitel, Osvaldo Daniel
author_role author
author2 Urbano Suarez, Francisco Jose
Di Guilmi, Mariano Nicolás
Ferrari, Michel D.
Van den Maagdenberg, Arn M. J. M.
Forsythe, Ian
Uchitel, Osvaldo Daniel
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv R192Q KI MICE
FAMILIAL HEMIPLEGIC MIGRAINE
CAV2.1 CALCIUM CHANNELS
EXCITATORY POSTSYNAPTIC CURRENTS
SHORT TERM SYNAPTIC PLASTICITY
topic R192Q KI MICE
FAMILIAL HEMIPLEGIC MIGRAINE
CAV2.1 CALCIUM CHANNELS
EXCITATORY POSTSYNAPTIC CURRENTS
SHORT TERM SYNAPTIC PLASTICITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv CaV2.1 Ca2+ channels have a dominant and specific role in initiating fast synaptic transmission at central excitatory synapses, through a close association between release sites and calcium sensors. Familial hemiplegic migraine type-1 (FHM-1) is an autosomal-dominant subtype of migraine with aura, caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 channel. We used knock-in (KI) transgenic mice harbouring the FHM-1 mutation R192Q to study the consequences of this mutation in neurotransmission at the giant synapse of the auditory system formed by the presynaptic calyx of Held terminal and the postsynaptic neurons of the Medial Nucleus of the Trapezoid Body (MNTB). Although synaptic transmission seems unaffected by low frequency stimulation in physiological Ca2+ concentration, we observed that with low Ca2+concentrations (< 1 mM) excitatory postsynaptic currents (EPSCs) showed increased amplitudes in R192Q KI mice compared to WT, meaning significant differences in the non-linear calcium-dependence of nerve-evoked transmitter release. In addition, when EPSCs were evoked by broadened presynaptic action potentials (achieved by inhibition of K+channels) via Cav2.1 triggered exocytosis, the R192Q KI mice exhibited further enhancement of EPSC amplitude and charge compared with WT mice. Repetitive stimulation of afferent axons to the MNTB at different frequencies caused short term depression of EPSCs that recovered significantly faster in R192Q KI than in WT mice. Faster recovery in R192Q KI mice was prevented by the calcium chelator EGTA-AM, pointing to enlarged residual calcium as a key factor in accelerating the replenishment of synaptic vesicles.
Fil: González Inchauspe, Carlota María Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Di Guilmi, Mariano Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Ferrari, Michel D.. Leiden University Medical Centre; Países Bajos
Fil: Van den Maagdenberg, Arn M. J. M.. Leiden University Medical Centre; Países Bajos
Fil: Forsythe, Ian. University of Leicester; Reino Unido
Fil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
description CaV2.1 Ca2+ channels have a dominant and specific role in initiating fast synaptic transmission at central excitatory synapses, through a close association between release sites and calcium sensors. Familial hemiplegic migraine type-1 (FHM-1) is an autosomal-dominant subtype of migraine with aura, caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 channel. We used knock-in (KI) transgenic mice harbouring the FHM-1 mutation R192Q to study the consequences of this mutation in neurotransmission at the giant synapse of the auditory system formed by the presynaptic calyx of Held terminal and the postsynaptic neurons of the Medial Nucleus of the Trapezoid Body (MNTB). Although synaptic transmission seems unaffected by low frequency stimulation in physiological Ca2+ concentration, we observed that with low Ca2+concentrations (< 1 mM) excitatory postsynaptic currents (EPSCs) showed increased amplitudes in R192Q KI mice compared to WT, meaning significant differences in the non-linear calcium-dependence of nerve-evoked transmitter release. In addition, when EPSCs were evoked by broadened presynaptic action potentials (achieved by inhibition of K+channels) via Cav2.1 triggered exocytosis, the R192Q KI mice exhibited further enhancement of EPSC amplitude and charge compared with WT mice. Repetitive stimulation of afferent axons to the MNTB at different frequencies caused short term depression of EPSCs that recovered significantly faster in R192Q KI than in WT mice. Faster recovery in R192Q KI mice was prevented by the calcium chelator EGTA-AM, pointing to enlarged residual calcium as a key factor in accelerating the replenishment of synaptic vesicles.
publishDate 2012
dc.date.none.fl_str_mv 2012-12
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/11336/85639
González Inchauspe, Carlota María Fabiola; Urbano Suarez, Francisco Jose; Di Guilmi, Mariano Nicolás; Ferrari, Michel D.; Van den Maagdenberg, Arn M. J. M.; et al.; Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held; American Physiological Society; Journal of Neurophysiology; 108; 11; 12-2012; 2967-2976
0022-3077
CONICET Digital
CONICET
url http://hdl.handle.net/11336/85639
identifier_str_mv González Inchauspe, Carlota María Fabiola; Urbano Suarez, Francisco Jose; Di Guilmi, Mariano Nicolás; Ferrari, Michel D.; Van den Maagdenberg, Arn M. J. M.; et al.; Presynaptic Cav2.1 calcium channels carrying a familial hemiplegic migraine mutation r192q allow faster recovery from syanptic depression in mouse calyx of held; American Physiological Society; Journal of Neurophysiology; 108; 11; 12-2012; 2967-2976
0022-3077
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/ 10.1152/jn.01183.2011
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/jn.01183.2011
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
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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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score 12.982451

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