Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential
- Autores
- González Inchauspe, Carlota María Fabiola; Urbano Suarez, Francisco Jose; Di Guilmi, Mariano Nicolás; Forsythe, Ian D.; Ferrari, Michel D.; Maagdenberg, Arn M. J. M. van den; Uchitel, Osvaldo Daniel
- Año de publicación
- 2010
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Familial hemiplegic migraine type-1 FHM-1 is caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 Ca2+ channels. We used knock-in (KI) transgenic mice harboring the pathogenic FHM-1 mutation R192Q to study neurotransmission at the calyx of Held synapse and cortical layer 2/3 pyramidal cells (PCs). Using whole cell patch-clamp recordings in brain stem slices, we confirmed that KI CaV2.1 Ca2+ channels activated at more hyperpolarizing potentials. However, calyceal presynaptic calcium currents (IpCa) evoked by presynaptic action potentials (APs) were similar in amplitude, kinetic parameters, and neurotransmitter release. CaV2.1 Ca2+ channels in cortical layer 2/3 PCs from KI mice also showed a negative shift in their activation voltage. PCs had APs with longer durations and smaller amplitudes than the calyx of Held. AP-evoked Ca2+ currents (I Ca) from PCs were larger in KI compared with wild-type (WT) mice. In contrast, when ICa was evoked in PCs by calyx of Held AP waveforms, we observed no amplitude differences between WT and KI mice. In the same way, Ca2+ currents evoked at the presynaptic terminals (IpCa)of the calyx of Held by the AP waveforms of the PCs had larger amplitudes in R192Q KI mice that in WT. These results suggest that longer time courses of pyramidal APs were a key factor for the expression of a synaptic gain of function in the KI mice. In addition, our results indicate that consequences of FHM-1 mutations might vary according to the shape of APs in charge of triggering synaptic transmission (neurons in the calyx of Held vs. excitatory/inhibitory neurons in the cortex), adding to the complexity of the pathophysiology of migraine.
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: Forsythe, Ian D.. University of Leicester; Reino Unido
Fil: Ferrari, Michel D.. Leiden University; Países Bajos
Fil: Maagdenberg, Arn M. J. M. van den. Leiden University; Países Bajos
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
-
Calcium Channels
Calyx of herld
Synapsis
Migrania - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/100022
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Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potentialGonzález Inchauspe, Carlota María FabiolaUrbano Suarez, Francisco JoseDi Guilmi, Mariano NicolásForsythe, Ian D.Ferrari, Michel D.Maagdenberg, Arn M. J. M. van denUchitel, Osvaldo DanielCalcium ChannelsCalyx of herldSynapsisMigraniahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Familial hemiplegic migraine type-1 FHM-1 is caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 Ca2+ channels. We used knock-in (KI) transgenic mice harboring the pathogenic FHM-1 mutation R192Q to study neurotransmission at the calyx of Held synapse and cortical layer 2/3 pyramidal cells (PCs). Using whole cell patch-clamp recordings in brain stem slices, we confirmed that KI CaV2.1 Ca2+ channels activated at more hyperpolarizing potentials. However, calyceal presynaptic calcium currents (IpCa) evoked by presynaptic action potentials (APs) were similar in amplitude, kinetic parameters, and neurotransmitter release. CaV2.1 Ca2+ channels in cortical layer 2/3 PCs from KI mice also showed a negative shift in their activation voltage. PCs had APs with longer durations and smaller amplitudes than the calyx of Held. AP-evoked Ca2+ currents (I Ca) from PCs were larger in KI compared with wild-type (WT) mice. In contrast, when ICa was evoked in PCs by calyx of Held AP waveforms, we observed no amplitude differences between WT and KI mice. In the same way, Ca2+ currents evoked at the presynaptic terminals (IpCa)of the calyx of Held by the AP waveforms of the PCs had larger amplitudes in R192Q KI mice that in WT. These results suggest that longer time courses of pyramidal APs were a key factor for the expression of a synaptic gain of function in the KI mice. In addition, our results indicate that consequences of FHM-1 mutations might vary according to the shape of APs in charge of triggering synaptic transmission (neurons in the calyx of Held vs. excitatory/inhibitory neurons in the cortex), adding to the complexity of the pathophysiology of migraine.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: Forsythe, Ian D.. University of Leicester; Reino UnidoFil: Ferrari, Michel D.. Leiden University; Países BajosFil: Maagdenberg, Arn M. J. M. van den. Leiden University; Países BajosFil: 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 Society2010-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/100022González Inchauspe, Carlota María Fabiola; Urbano Suarez, Francisco Jose; Di Guilmi, Mariano Nicolás; Forsythe, Ian D.; Ferrari, Michel D.; et al.; Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential; American Physiological Society; Journal of Neurophysiology; 104; 1; 7-2010; 291-2990022-3077CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1152/jn.00034.2010info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904224/info:eu-repo/semantics/altIdentifier/url/https://journals.physiology.org/doi/full/10.1152/jn.00034.2010info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:49:40Zoai:ri.conicet.gov.ar:11336/100022instacron: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:34982025-09-29 09:49:41.145CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential |
title |
Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential |
spellingShingle |
Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential González Inchauspe, Carlota María Fabiola Calcium Channels Calyx of herld Synapsis Migrania |
title_short |
Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential |
title_full |
Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential |
title_fullStr |
Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential |
title_full_unstemmed |
Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential |
title_sort |
Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential |
dc.creator.none.fl_str_mv |
González Inchauspe, Carlota María Fabiola Urbano Suarez, Francisco Jose Di Guilmi, Mariano Nicolás Forsythe, Ian D. Ferrari, Michel D. Maagdenberg, Arn M. J. M. van den Uchitel, Osvaldo Daniel |
author |
González Inchauspe, Carlota María Fabiola |
author_facet |
González Inchauspe, Carlota María Fabiola Urbano Suarez, Francisco Jose Di Guilmi, Mariano Nicolás Forsythe, Ian D. Ferrari, Michel D. Maagdenberg, Arn M. J. M. van den Uchitel, Osvaldo Daniel |
author_role |
author |
author2 |
Urbano Suarez, Francisco Jose Di Guilmi, Mariano Nicolás Forsythe, Ian D. Ferrari, Michel D. Maagdenberg, Arn M. J. M. van den Uchitel, Osvaldo Daniel |
author2_role |
author author author author author author |
dc.subject.none.fl_str_mv |
Calcium Channels Calyx of herld Synapsis Migrania |
topic |
Calcium Channels Calyx of herld Synapsis Migrania |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Familial hemiplegic migraine type-1 FHM-1 is caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 Ca2+ channels. We used knock-in (KI) transgenic mice harboring the pathogenic FHM-1 mutation R192Q to study neurotransmission at the calyx of Held synapse and cortical layer 2/3 pyramidal cells (PCs). Using whole cell patch-clamp recordings in brain stem slices, we confirmed that KI CaV2.1 Ca2+ channels activated at more hyperpolarizing potentials. However, calyceal presynaptic calcium currents (IpCa) evoked by presynaptic action potentials (APs) were similar in amplitude, kinetic parameters, and neurotransmitter release. CaV2.1 Ca2+ channels in cortical layer 2/3 PCs from KI mice also showed a negative shift in their activation voltage. PCs had APs with longer durations and smaller amplitudes than the calyx of Held. AP-evoked Ca2+ currents (I Ca) from PCs were larger in KI compared with wild-type (WT) mice. In contrast, when ICa was evoked in PCs by calyx of Held AP waveforms, we observed no amplitude differences between WT and KI mice. In the same way, Ca2+ currents evoked at the presynaptic terminals (IpCa)of the calyx of Held by the AP waveforms of the PCs had larger amplitudes in R192Q KI mice that in WT. These results suggest that longer time courses of pyramidal APs were a key factor for the expression of a synaptic gain of function in the KI mice. In addition, our results indicate that consequences of FHM-1 mutations might vary according to the shape of APs in charge of triggering synaptic transmission (neurons in the calyx of Held vs. excitatory/inhibitory neurons in the cortex), adding to the complexity of the pathophysiology of migraine. 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: Forsythe, Ian D.. University of Leicester; Reino Unido Fil: Ferrari, Michel D.. Leiden University; Países Bajos Fil: Maagdenberg, Arn M. J. M. van den. Leiden University; Países Bajos 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 |
Familial hemiplegic migraine type-1 FHM-1 is caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 Ca2+ channels. We used knock-in (KI) transgenic mice harboring the pathogenic FHM-1 mutation R192Q to study neurotransmission at the calyx of Held synapse and cortical layer 2/3 pyramidal cells (PCs). Using whole cell patch-clamp recordings in brain stem slices, we confirmed that KI CaV2.1 Ca2+ channels activated at more hyperpolarizing potentials. However, calyceal presynaptic calcium currents (IpCa) evoked by presynaptic action potentials (APs) were similar in amplitude, kinetic parameters, and neurotransmitter release. CaV2.1 Ca2+ channels in cortical layer 2/3 PCs from KI mice also showed a negative shift in their activation voltage. PCs had APs with longer durations and smaller amplitudes than the calyx of Held. AP-evoked Ca2+ currents (I Ca) from PCs were larger in KI compared with wild-type (WT) mice. In contrast, when ICa was evoked in PCs by calyx of Held AP waveforms, we observed no amplitude differences between WT and KI mice. In the same way, Ca2+ currents evoked at the presynaptic terminals (IpCa)of the calyx of Held by the AP waveforms of the PCs had larger amplitudes in R192Q KI mice that in WT. These results suggest that longer time courses of pyramidal APs were a key factor for the expression of a synaptic gain of function in the KI mice. In addition, our results indicate that consequences of FHM-1 mutations might vary according to the shape of APs in charge of triggering synaptic transmission (neurons in the calyx of Held vs. excitatory/inhibitory neurons in the cortex), adding to the complexity of the pathophysiology of migraine. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-07 |
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/11336/100022 González Inchauspe, Carlota María Fabiola; Urbano Suarez, Francisco Jose; Di Guilmi, Mariano Nicolás; Forsythe, Ian D.; Ferrari, Michel D.; et al.; Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential; American Physiological Society; Journal of Neurophysiology; 104; 1; 7-2010; 291-299 0022-3077 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/100022 |
identifier_str_mv |
González Inchauspe, Carlota María Fabiola; Urbano Suarez, Francisco Jose; Di Guilmi, Mariano Nicolás; Forsythe, Ian D.; Ferrari, Michel D.; et al.; Gain of function in FHM-1 Cav2.1 knock-in mice is related to the shape of the action potential; American Physiological Society; Journal of Neurophysiology; 104; 1; 7-2010; 291-299 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.00034.2010 info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904224/ info:eu-repo/semantics/altIdentifier/url/https://journals.physiology.org/doi/full/10.1152/jn.00034.2010 |
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 |
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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.070432 |