Redox modulation of homomeric ρ1 GABAC receptors

Autores
Calero, Cecilia Ines; Calvo, Daniel Juan
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The activity of many receptors and ion channels in the nervous system can be regulated by redox-dependent mechanisms. Native and recombinant GABA A receptors are modulated by endogenous and pharmacological redox agents. However, the sensitivity of GABAC receptors to redox modulation has not been demonstrated. We studied the actions of different reducing and oxidizing agents on human homomeric GABAρ1 receptors expressed in Xenopus laevis oocytes. The reducing agents dithiothreitol (2 mM) and N-acetyl-l-cysteine (1 mM) potentiated GABA-evoked Cl- currents recorded by two-electrode voltage-clamp, while the oxidants 5-5′- dithiobis-2-nitrobenzoic acid (500 μM) and oxidized dithiothreitol (2 mM) caused inhibition. The endogenous antioxidant glutathione (5 mM) also enhanced GABAρ1 receptor-mediated currents while its oxidized form GSSG (3 mM) had inhibitory effects. All the effects were rapid and easily reversible. Redox modulation of GABAρ1 receptors was strongly dependent on the GABA concentration; dose-response curves for GABA were shifted to the left in the presence of reducing agents, whereas oxidizing agents produced the opposite effect, without changes in the maximal response to GABA and in the Hill coefficient. Our results demonstrate that, similarly to GABAA receptors and other members of the cys-loop receptor superfamily, GABA C receptors are subjected to redox modulation.
Fil: Calero, Cecilia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Materia
Antioxidants
Chloride Currents
Cys-Loop Receptors
Gabac Receptors
Redox Modulation
Retina
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:11336/79699
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/79699
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Redox modulation of homomeric ρ1 GABAC receptorsCalero, Cecilia InesCalvo, Daniel JuanAntioxidantsChloride CurrentsCys-Loop ReceptorsGabac ReceptorsRedox ModulationRetinahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The activity of many receptors and ion channels in the nervous system can be regulated by redox-dependent mechanisms. Native and recombinant GABA A receptors are modulated by endogenous and pharmacological redox agents. However, the sensitivity of GABAC receptors to redox modulation has not been demonstrated. We studied the actions of different reducing and oxidizing agents on human homomeric GABAρ1 receptors expressed in Xenopus laevis oocytes. The reducing agents dithiothreitol (2 mM) and N-acetyl-l-cysteine (1 mM) potentiated GABA-evoked Cl- currents recorded by two-electrode voltage-clamp, while the oxidants 5-5′- dithiobis-2-nitrobenzoic acid (500 μM) and oxidized dithiothreitol (2 mM) caused inhibition. The endogenous antioxidant glutathione (5 mM) also enhanced GABAρ1 receptor-mediated currents while its oxidized form GSSG (3 mM) had inhibitory effects. All the effects were rapid and easily reversible. Redox modulation of GABAρ1 receptors was strongly dependent on the GABA concentration; dose-response curves for GABA were shifted to the left in the presence of reducing agents, whereas oxidizing agents produced the opposite effect, without changes in the maximal response to GABA and in the Hill coefficient. Our results demonstrate that, similarly to GABAA receptors and other members of the cys-loop receptor superfamily, GABA C receptors are subjected to redox modulation.Fil: Calero, Cecilia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaWiley Blackwell Publishing, Inc2008-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79699Calero, Cecilia Ines; Calvo, Daniel Juan; Redox modulation of homomeric ρ1 GABAC receptors; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 105; 6; 6-2008; 2367-23740022-3042CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1471-4159.2008.05319.xinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1111/j.1471-4159.2008.05319.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:41:03Zoai:ri.conicet.gov.ar:11336/79699instacron: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 10:41:03.476CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Redox modulation of homomeric ρ1 GABAC receptors
title Redox modulation of homomeric ρ1 GABAC receptors
spellingShingle Redox modulation of homomeric ρ1 GABAC receptors
Calero, Cecilia Ines
Antioxidants
Chloride Currents
Cys-Loop Receptors
Gabac Receptors
Redox Modulation
Retina
title_short Redox modulation of homomeric ρ1 GABAC receptors
title_full Redox modulation of homomeric ρ1 GABAC receptors
title_fullStr Redox modulation of homomeric ρ1 GABAC receptors
title_full_unstemmed Redox modulation of homomeric ρ1 GABAC receptors
title_sort Redox modulation of homomeric ρ1 GABAC receptors
dc.creator.none.fl_str_mv Calero, Cecilia Ines
Calvo, Daniel Juan
author Calero, Cecilia Ines
author_facet Calero, Cecilia Ines
Calvo, Daniel Juan
author_role author
author2 Calvo, Daniel Juan
author2_role author
dc.subject.none.fl_str_mv Antioxidants
Chloride Currents
Cys-Loop Receptors
Gabac Receptors
Redox Modulation
Retina
topic Antioxidants
Chloride Currents
Cys-Loop Receptors
Gabac Receptors
Redox Modulation
Retina
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The activity of many receptors and ion channels in the nervous system can be regulated by redox-dependent mechanisms. Native and recombinant GABA A receptors are modulated by endogenous and pharmacological redox agents. However, the sensitivity of GABAC receptors to redox modulation has not been demonstrated. We studied the actions of different reducing and oxidizing agents on human homomeric GABAρ1 receptors expressed in Xenopus laevis oocytes. The reducing agents dithiothreitol (2 mM) and N-acetyl-l-cysteine (1 mM) potentiated GABA-evoked Cl- currents recorded by two-electrode voltage-clamp, while the oxidants 5-5′- dithiobis-2-nitrobenzoic acid (500 μM) and oxidized dithiothreitol (2 mM) caused inhibition. The endogenous antioxidant glutathione (5 mM) also enhanced GABAρ1 receptor-mediated currents while its oxidized form GSSG (3 mM) had inhibitory effects. All the effects were rapid and easily reversible. Redox modulation of GABAρ1 receptors was strongly dependent on the GABA concentration; dose-response curves for GABA were shifted to the left in the presence of reducing agents, whereas oxidizing agents produced the opposite effect, without changes in the maximal response to GABA and in the Hill coefficient. Our results demonstrate that, similarly to GABAA receptors and other members of the cys-loop receptor superfamily, GABA C receptors are subjected to redox modulation.
Fil: Calero, Cecilia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
description The activity of many receptors and ion channels in the nervous system can be regulated by redox-dependent mechanisms. Native and recombinant GABA A receptors are modulated by endogenous and pharmacological redox agents. However, the sensitivity of GABAC receptors to redox modulation has not been demonstrated. We studied the actions of different reducing and oxidizing agents on human homomeric GABAρ1 receptors expressed in Xenopus laevis oocytes. The reducing agents dithiothreitol (2 mM) and N-acetyl-l-cysteine (1 mM) potentiated GABA-evoked Cl- currents recorded by two-electrode voltage-clamp, while the oxidants 5-5′- dithiobis-2-nitrobenzoic acid (500 μM) and oxidized dithiothreitol (2 mM) caused inhibition. The endogenous antioxidant glutathione (5 mM) also enhanced GABAρ1 receptor-mediated currents while its oxidized form GSSG (3 mM) had inhibitory effects. All the effects were rapid and easily reversible. Redox modulation of GABAρ1 receptors was strongly dependent on the GABA concentration; dose-response curves for GABA were shifted to the left in the presence of reducing agents, whereas oxidizing agents produced the opposite effect, without changes in the maximal response to GABA and in the Hill coefficient. Our results demonstrate that, similarly to GABAA receptors and other members of the cys-loop receptor superfamily, GABA C receptors are subjected to redox modulation.
publishDate 2008
dc.date.none.fl_str_mv 2008-06
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/11336/79699
Calero, Cecilia Ines; Calvo, Daniel Juan; Redox modulation of homomeric ρ1 GABAC receptors; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 105; 6; 6-2008; 2367-2374
0022-3042
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79699
identifier_str_mv Calero, Cecilia Ines; Calvo, Daniel Juan; Redox modulation of homomeric ρ1 GABAC receptors; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 105; 6; 6-2008; 2367-2374
0022-3042
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1471-4159.2008.05319.x
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1111/j.1471-4159.2008.05319.x
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 Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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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