Stoichiometry for activation of neuronal α7 nicotinic Receptors

Autores
Andersen, Natalia Denise; Corradi, Jeremias; Sine, Steve; Bouzat, Cecilia Beatriz
Año de publicación
2013
Idioma
español castellano
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Neuronal α7 nicotinic receptors are homopentameric ligand-gated ion channels (LGICs) that participate in cognition, synaptic plasticity and neuroprotection, and have emerged as therapeutic targets for treatment of neurological disorders. α7 often localizes distal to sites of nerve-released ACh, binds ACh with low affinity, and thus elicits its biological response with partial occupancy of its five identical binding sites. We therefore addressed the question of how α7 operates at these physiological conditions. To assess function of α7 when neurotransmitter occupies fewer than five binding sites, we generated α7 receptors with a different number of functional neurotransmitter binding sites. By measuring open-channel lifetime of individual receptors, we found that only one occupied site allows maximal response and that the additional sites allow enhanced agonist sensitivity. In contrast to α7, we found that open-channel lifetime of a receptor formed by the extracellular domain of α7 and the transmembrane region of 5-HT3A (α7-5HT3A) is dependent on the number of functional binding sites. Our results reveal that: i) the agonist binding domain is not sufficient to determine the relationship between agonist occupancy and open-channel stability and, ii) the distinctive ability of a single occupancy to elicit a full biological response adapts α7 to volume transmission, a prevalent mechanism of ACh-mediated signaling in the nervous system and non-neuronal cells.
Fil: Andersen, Natalia Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Corradi, Jeremias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Sine, Steve. Mayo Clinic College of Medicine; Estados Unidos
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.
Huerta Grande
Argentina
Sociedad Argentina de Neurociencias
Materia
PATCH-CLAMP
RECEPTORS
BINDING
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:11336/222948
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Stoichiometry for activation of neuronal α7 nicotinic ReceptorsAndersen, Natalia DeniseCorradi, JeremiasSine, SteveBouzat, Cecilia BeatrizPATCH-CLAMPRECEPTORSBINDINGhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Neuronal α7 nicotinic receptors are homopentameric ligand-gated ion channels (LGICs) that participate in cognition, synaptic plasticity and neuroprotection, and have emerged as therapeutic targets for treatment of neurological disorders. α7 often localizes distal to sites of nerve-released ACh, binds ACh with low affinity, and thus elicits its biological response with partial occupancy of its five identical binding sites. We therefore addressed the question of how α7 operates at these physiological conditions. To assess function of α7 when neurotransmitter occupies fewer than five binding sites, we generated α7 receptors with a different number of functional neurotransmitter binding sites. By measuring open-channel lifetime of individual receptors, we found that only one occupied site allows maximal response and that the additional sites allow enhanced agonist sensitivity. In contrast to α7, we found that open-channel lifetime of a receptor formed by the extracellular domain of α7 and the transmembrane region of 5-HT3A (α7-5HT3A) is dependent on the number of functional binding sites. Our results reveal that: i) the agonist binding domain is not sufficient to determine the relationship between agonist occupancy and open-channel stability and, ii) the distinctive ability of a single occupancy to elicit a full biological response adapts α7 to volume transmission, a prevalent mechanism of ACh-mediated signaling in the nervous system and non-neuronal cells.Fil: Andersen, Natalia Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Corradi, Jeremias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Sine, Steve. Mayo Clinic College of Medicine; Estados UnidosFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaXXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.Huerta GrandeArgentinaSociedad Argentina de NeurocienciasSociedad Argentina de Investigación en Neurociencias2013info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/222948Stoichiometry for activation of neuronal α7 nicotinic Receptors; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.; Huerta Grande; Argentina; 2013; 285-285CONICET DigitalCONICETspainfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/congresos-san-2/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:56:27Zoai:ri.conicet.gov.ar:11336/222948instacron: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:34982025-10-15 14:56:27.331CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Stoichiometry for activation of neuronal α7 nicotinic Receptors
title Stoichiometry for activation of neuronal α7 nicotinic Receptors
spellingShingle Stoichiometry for activation of neuronal α7 nicotinic Receptors
Andersen, Natalia Denise
PATCH-CLAMP
RECEPTORS
BINDING
title_short Stoichiometry for activation of neuronal α7 nicotinic Receptors
title_full Stoichiometry for activation of neuronal α7 nicotinic Receptors
title_fullStr Stoichiometry for activation of neuronal α7 nicotinic Receptors
title_full_unstemmed Stoichiometry for activation of neuronal α7 nicotinic Receptors
title_sort Stoichiometry for activation of neuronal α7 nicotinic Receptors
dc.creator.none.fl_str_mv Andersen, Natalia Denise
Corradi, Jeremias
Sine, Steve
Bouzat, Cecilia Beatriz
author Andersen, Natalia Denise
author_facet Andersen, Natalia Denise
Corradi, Jeremias
Sine, Steve
Bouzat, Cecilia Beatriz
author_role author
author2 Corradi, Jeremias
Sine, Steve
Bouzat, Cecilia Beatriz
author2_role author
author
author
dc.subject.none.fl_str_mv PATCH-CLAMP
RECEPTORS
BINDING
topic PATCH-CLAMP
RECEPTORS
BINDING
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Neuronal α7 nicotinic receptors are homopentameric ligand-gated ion channels (LGICs) that participate in cognition, synaptic plasticity and neuroprotection, and have emerged as therapeutic targets for treatment of neurological disorders. α7 often localizes distal to sites of nerve-released ACh, binds ACh with low affinity, and thus elicits its biological response with partial occupancy of its five identical binding sites. We therefore addressed the question of how α7 operates at these physiological conditions. To assess function of α7 when neurotransmitter occupies fewer than five binding sites, we generated α7 receptors with a different number of functional neurotransmitter binding sites. By measuring open-channel lifetime of individual receptors, we found that only one occupied site allows maximal response and that the additional sites allow enhanced agonist sensitivity. In contrast to α7, we found that open-channel lifetime of a receptor formed by the extracellular domain of α7 and the transmembrane region of 5-HT3A (α7-5HT3A) is dependent on the number of functional binding sites. Our results reveal that: i) the agonist binding domain is not sufficient to determine the relationship between agonist occupancy and open-channel stability and, ii) the distinctive ability of a single occupancy to elicit a full biological response adapts α7 to volume transmission, a prevalent mechanism of ACh-mediated signaling in the nervous system and non-neuronal cells.
Fil: Andersen, Natalia Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Corradi, Jeremias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Sine, Steve. Mayo Clinic College of Medicine; Estados Unidos
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.
Huerta Grande
Argentina
Sociedad Argentina de Neurociencias
description Neuronal α7 nicotinic receptors are homopentameric ligand-gated ion channels (LGICs) that participate in cognition, synaptic plasticity and neuroprotection, and have emerged as therapeutic targets for treatment of neurological disorders. α7 often localizes distal to sites of nerve-released ACh, binds ACh with low affinity, and thus elicits its biological response with partial occupancy of its five identical binding sites. We therefore addressed the question of how α7 operates at these physiological conditions. To assess function of α7 when neurotransmitter occupies fewer than five binding sites, we generated α7 receptors with a different number of functional neurotransmitter binding sites. By measuring open-channel lifetime of individual receptors, we found that only one occupied site allows maximal response and that the additional sites allow enhanced agonist sensitivity. In contrast to α7, we found that open-channel lifetime of a receptor formed by the extracellular domain of α7 and the transmembrane region of 5-HT3A (α7-5HT3A) is dependent on the number of functional binding sites. Our results reveal that: i) the agonist binding domain is not sufficient to determine the relationship between agonist occupancy and open-channel stability and, ii) the distinctive ability of a single occupancy to elicit a full biological response adapts α7 to volume transmission, a prevalent mechanism of ACh-mediated signaling in the nervous system and non-neuronal cells.
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/222948
Stoichiometry for activation of neuronal α7 nicotinic Receptors; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.; Huerta Grande; Argentina; 2013; 285-285
CONICET Digital
CONICET
url http://hdl.handle.net/11336/222948
identifier_str_mv Stoichiometry for activation of neuronal α7 nicotinic Receptors; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.; Huerta Grande; Argentina; 2013; 285-285
CONICET Digital
CONICET
dc.language.none.fl_str_mv spa
language spa
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/congresos-san-2/
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
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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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 13.221938

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