Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels

Autores
Di Guilmi, Mariano Nicolás; Urbano Suarez, Francisco Jose; González Inchauspe, Carlota María Fabiola; Uchitel, Osvaldo Daniel
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In this work, we studied the effects of the anticonvulsant and analgesic drug pregabalin (PGB) on excitatory postsynaptic currents (EPSCs) at principal neurons of the mouse medial nucleus of the trapezoid body and on presynaptic calcium currents at the calyx of Held. We found that the acute application of PGB reduced the amplitude of EPSCs in a dose-dependent manner with a maximal blocking effect of approximately 30%. A clinical high-concentration dose of PGB (e.g., 500 μM) blocked Cav2.1 channel-mediated currents and decreased their facilitation during a 100-Hz train, without changing their voltage-dependent activation. Furthermore, PGB also removed the inactivation of Cav2.1 channels at a clinically relevant low concentration of 100 μM. These results suggest novel modulatory mechanisms mediated by the acute administration of PGB on fast excitatory synaptic transmission and might contribute to better understanding PGB anticonvulsant/analgesic clinical effects.
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: 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: 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: 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
PREGABALIN
CALYX OF HELD
CALCIUM CHANNELS
P/Q-TYPE
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:11336/98640
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/98640
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channelsDi Guilmi, Mariano NicolásUrbano Suarez, Francisco JoseGonzález Inchauspe, Carlota María FabiolaUchitel, Osvaldo DanielPREGABALINCALYX OF HELDCALCIUM CHANNELSP/Q-TYPEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In this work, we studied the effects of the anticonvulsant and analgesic drug pregabalin (PGB) on excitatory postsynaptic currents (EPSCs) at principal neurons of the mouse medial nucleus of the trapezoid body and on presynaptic calcium currents at the calyx of Held. We found that the acute application of PGB reduced the amplitude of EPSCs in a dose-dependent manner with a maximal blocking effect of approximately 30%. A clinical high-concentration dose of PGB (e.g., 500 μM) blocked Cav2.1 channel-mediated currents and decreased their facilitation during a 100-Hz train, without changing their voltage-dependent activation. Furthermore, PGB also removed the inactivation of Cav2.1 channels at a clinically relevant low concentration of 100 μM. These results suggest novel modulatory mechanisms mediated by the acute administration of PGB on fast excitatory synaptic transmission and might contribute to better understanding PGB anticonvulsant/analgesic clinical effects.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; 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: 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: 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 Society for Pharmacology and Experimental Therapeutics2011-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/98640Di Guilmi, Mariano Nicolás; Urbano Suarez, Francisco Jose; González Inchauspe, Carlota María Fabiola; Uchitel, Osvaldo Daniel; Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels; American Society for Pharmacology and Experimental Therapeutics; Journal of Pharmacology and Experimental Therapeutics; 336; 3; 3-2011; 973-9820022-3565CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://jpet.aspetjournals.org/content/336/3/973info:eu-repo/semantics/altIdentifier/doi/10.1124/jpet.110.172171info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:07:30Zoai:ri.conicet.gov.ar:11336/98640instacron: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 10:07:30.96CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels
title Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels
spellingShingle Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels
Di Guilmi, Mariano Nicolás
PREGABALIN
CALYX OF HELD
CALCIUM CHANNELS
P/Q-TYPE
title_short Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels
title_full Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels
title_fullStr Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels
title_full_unstemmed Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels
title_sort Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels
dc.creator.none.fl_str_mv Di Guilmi, Mariano Nicolás
Urbano Suarez, Francisco Jose
González Inchauspe, Carlota María Fabiola
Uchitel, Osvaldo Daniel
author Di Guilmi, Mariano Nicolás
author_facet Di Guilmi, Mariano Nicolás
Urbano Suarez, Francisco Jose
González Inchauspe, Carlota María Fabiola
Uchitel, Osvaldo Daniel
author_role author
author2 Urbano Suarez, Francisco Jose
González Inchauspe, Carlota María Fabiola
Uchitel, Osvaldo Daniel
author2_role author
author
author
dc.subject.none.fl_str_mv PREGABALIN
CALYX OF HELD
CALCIUM CHANNELS
P/Q-TYPE
topic PREGABALIN
CALYX OF HELD
CALCIUM CHANNELS
P/Q-TYPE
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 this work, we studied the effects of the anticonvulsant and analgesic drug pregabalin (PGB) on excitatory postsynaptic currents (EPSCs) at principal neurons of the mouse medial nucleus of the trapezoid body and on presynaptic calcium currents at the calyx of Held. We found that the acute application of PGB reduced the amplitude of EPSCs in a dose-dependent manner with a maximal blocking effect of approximately 30%. A clinical high-concentration dose of PGB (e.g., 500 μM) blocked Cav2.1 channel-mediated currents and decreased their facilitation during a 100-Hz train, without changing their voltage-dependent activation. Furthermore, PGB also removed the inactivation of Cav2.1 channels at a clinically relevant low concentration of 100 μM. These results suggest novel modulatory mechanisms mediated by the acute administration of PGB on fast excitatory synaptic transmission and might contribute to better understanding PGB anticonvulsant/analgesic clinical effects.
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: 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: 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: 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 In this work, we studied the effects of the anticonvulsant and analgesic drug pregabalin (PGB) on excitatory postsynaptic currents (EPSCs) at principal neurons of the mouse medial nucleus of the trapezoid body and on presynaptic calcium currents at the calyx of Held. We found that the acute application of PGB reduced the amplitude of EPSCs in a dose-dependent manner with a maximal blocking effect of approximately 30%. A clinical high-concentration dose of PGB (e.g., 500 μM) blocked Cav2.1 channel-mediated currents and decreased their facilitation during a 100-Hz train, without changing their voltage-dependent activation. Furthermore, PGB also removed the inactivation of Cav2.1 channels at a clinically relevant low concentration of 100 μM. These results suggest novel modulatory mechanisms mediated by the acute administration of PGB on fast excitatory synaptic transmission and might contribute to better understanding PGB anticonvulsant/analgesic clinical effects.
publishDate 2011
dc.date.none.fl_str_mv 2011-03
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/11336/98640
Di Guilmi, Mariano Nicolás; Urbano Suarez, Francisco Jose; González Inchauspe, Carlota María Fabiola; Uchitel, Osvaldo Daniel; Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels; American Society for Pharmacology and Experimental Therapeutics; Journal of Pharmacology and Experimental Therapeutics; 336; 3; 3-2011; 973-982
0022-3565
CONICET Digital
CONICET
url http://hdl.handle.net/11336/98640
identifier_str_mv Di Guilmi, Mariano Nicolás; Urbano Suarez, Francisco Jose; González Inchauspe, Carlota María Fabiola; Uchitel, Osvaldo Daniel; Pregabalin modulation of neurotransmitter release is mediated by change in intrinsic activation/inactivation properties of Cav2.1 calcium channels; American Society for Pharmacology and Experimental Therapeutics; Journal of Pharmacology and Experimental Therapeutics; 336; 3; 3-2011; 973-982
0022-3565
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://jpet.aspetjournals.org/content/336/3/973
info:eu-repo/semantics/altIdentifier/doi/10.1124/jpet.110.172171
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 Society for Pharmacology and Experimental Therapeutics
publisher.none.fl_str_mv American Society for Pharmacology and Experimental Therapeutics
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 13.070432

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