A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone

Autores
Corradi, Jeremias; Andersen, Natalia Denise; Bouzat, Cecilia Beatriz
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Modulation of Cys-loop receptors by steroids is of physiological and therapeutical relevance. Nonetheless, its molecular mechanism has not been elucidated for serotonin (5-HT) type 3 receptors. We deciphered the mechanism of action of hydrocortisone (HC) at 5-HT type 3A receptors. Single-channel currents from the high-conductance form (∼4.7 pA, −70 mV) appear as a series of long opening events forming bursts, which group into long clusters. Although they are very infrequent, subconductance events (∼2.4 pA) are detected within clusters. HC produces a significant concentration-dependent reduction in open and burst durations, demonstrating open-channel block. In addition, it increases the appearance of subconductance levels in a concentration- and slightly voltage-dependent manner. The amplitude of the subconductance level does not change with HC concentration and its open duration is briefer than that of full amplitude events, indicating lower open-channel stability. Dual effects are distinguished from macroscopic responses: HC reduces amplitude by acting from either open or closed states, and it increases decay rates from the open state. Thus, HC acts as a negative modulator of 5-HT type 3A receptors by different mechanisms: It acts as an open-channel blocker and it favors opening to a preexisting subconductance level. The latter constitutes a novel, to our knowledge, mechanism of channel modulation, which might be applicable to other steroids and channels.
Fil: Corradi, Jeremias. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Andersen, Natalia Denise. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Materia
5-Ht3 Receptor
Steroids
Ligand-Gated Ion Channels
Patch-Clamp
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/6459
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/6459
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A Novel Mechanism of Modulation of 5-HT3A Receptors by HydrocortisoneCorradi, JeremiasAndersen, Natalia DeniseBouzat, Cecilia Beatriz5-Ht3 ReceptorSteroidsLigand-Gated Ion ChannelsPatch-Clamphttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Modulation of Cys-loop receptors by steroids is of physiological and therapeutical relevance. Nonetheless, its molecular mechanism has not been elucidated for serotonin (5-HT) type 3 receptors. We deciphered the mechanism of action of hydrocortisone (HC) at 5-HT type 3A receptors. Single-channel currents from the high-conductance form (∼4.7 pA, −70 mV) appear as a series of long opening events forming bursts, which group into long clusters. Although they are very infrequent, subconductance events (∼2.4 pA) are detected within clusters. HC produces a significant concentration-dependent reduction in open and burst durations, demonstrating open-channel block. In addition, it increases the appearance of subconductance levels in a concentration- and slightly voltage-dependent manner. The amplitude of the subconductance level does not change with HC concentration and its open duration is briefer than that of full amplitude events, indicating lower open-channel stability. Dual effects are distinguished from macroscopic responses: HC reduces amplitude by acting from either open or closed states, and it increases decay rates from the open state. Thus, HC acts as a negative modulator of 5-HT type 3A receptors by different mechanisms: It acts as an open-channel blocker and it favors opening to a preexisting subconductance level. The latter constitutes a novel, to our knowledge, mechanism of channel modulation, which might be applicable to other steroids and channels.Fil: Corradi, Jeremias. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Andersen, Natalia Denise. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaCell Press2011-01info: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/11336/6459Corradi, Jeremias; Andersen, Natalia Denise; Bouzat, Cecilia Beatriz; A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone; Cell Press; Biophysical Journal; 100; 1; 1-2011; 42-510006-3495enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bpj.2010.10.046info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006349510013640info:eu-repo/semantics/altIdentifier/url/http://www.cell.com/biophysj/abstract/S0006-3495(10)01364-0info:eu-repo/semantics/altIdentifier/pmid/PMC3010835info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010835/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:34:08Zoai:ri.conicet.gov.ar:11336/6459instacron: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:34982025-11-12 09:34:08.983CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone
title A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone
spellingShingle A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone
Corradi, Jeremias
5-Ht3 Receptor
Steroids
Ligand-Gated Ion Channels
Patch-Clamp
title_short A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone
title_full A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone
title_fullStr A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone
title_full_unstemmed A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone
title_sort A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone
dc.creator.none.fl_str_mv Corradi, Jeremias
Andersen, Natalia Denise
Bouzat, Cecilia Beatriz
author Corradi, Jeremias
author_facet Corradi, Jeremias
Andersen, Natalia Denise
Bouzat, Cecilia Beatriz
author_role author
author2 Andersen, Natalia Denise
Bouzat, Cecilia Beatriz
author2_role author
author
dc.subject.none.fl_str_mv 5-Ht3 Receptor
Steroids
Ligand-Gated Ion Channels
Patch-Clamp
topic 5-Ht3 Receptor
Steroids
Ligand-Gated Ion Channels
Patch-Clamp
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Modulation of Cys-loop receptors by steroids is of physiological and therapeutical relevance. Nonetheless, its molecular mechanism has not been elucidated for serotonin (5-HT) type 3 receptors. We deciphered the mechanism of action of hydrocortisone (HC) at 5-HT type 3A receptors. Single-channel currents from the high-conductance form (∼4.7 pA, −70 mV) appear as a series of long opening events forming bursts, which group into long clusters. Although they are very infrequent, subconductance events (∼2.4 pA) are detected within clusters. HC produces a significant concentration-dependent reduction in open and burst durations, demonstrating open-channel block. In addition, it increases the appearance of subconductance levels in a concentration- and slightly voltage-dependent manner. The amplitude of the subconductance level does not change with HC concentration and its open duration is briefer than that of full amplitude events, indicating lower open-channel stability. Dual effects are distinguished from macroscopic responses: HC reduces amplitude by acting from either open or closed states, and it increases decay rates from the open state. Thus, HC acts as a negative modulator of 5-HT type 3A receptors by different mechanisms: It acts as an open-channel blocker and it favors opening to a preexisting subconductance level. The latter constitutes a novel, to our knowledge, mechanism of channel modulation, which might be applicable to other steroids and channels.
Fil: Corradi, Jeremias. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Andersen, Natalia Denise. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
description Modulation of Cys-loop receptors by steroids is of physiological and therapeutical relevance. Nonetheless, its molecular mechanism has not been elucidated for serotonin (5-HT) type 3 receptors. We deciphered the mechanism of action of hydrocortisone (HC) at 5-HT type 3A receptors. Single-channel currents from the high-conductance form (∼4.7 pA, −70 mV) appear as a series of long opening events forming bursts, which group into long clusters. Although they are very infrequent, subconductance events (∼2.4 pA) are detected within clusters. HC produces a significant concentration-dependent reduction in open and burst durations, demonstrating open-channel block. In addition, it increases the appearance of subconductance levels in a concentration- and slightly voltage-dependent manner. The amplitude of the subconductance level does not change with HC concentration and its open duration is briefer than that of full amplitude events, indicating lower open-channel stability. Dual effects are distinguished from macroscopic responses: HC reduces amplitude by acting from either open or closed states, and it increases decay rates from the open state. Thus, HC acts as a negative modulator of 5-HT type 3A receptors by different mechanisms: It acts as an open-channel blocker and it favors opening to a preexisting subconductance level. The latter constitutes a novel, to our knowledge, mechanism of channel modulation, which might be applicable to other steroids and channels.
publishDate 2011
dc.date.none.fl_str_mv 2011-01
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/11336/6459
Corradi, Jeremias; Andersen, Natalia Denise; Bouzat, Cecilia Beatriz; A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone; Cell Press; Biophysical Journal; 100; 1; 1-2011; 42-51
0006-3495
url http://hdl.handle.net/11336/6459
identifier_str_mv Corradi, Jeremias; Andersen, Natalia Denise; Bouzat, Cecilia Beatriz; A Novel Mechanism of Modulation of 5-HT3A Receptors by Hydrocortisone; Cell Press; Biophysical Journal; 100; 1; 1-2011; 42-51
0006-3495
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bpj.2010.10.046
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006349510013640
info:eu-repo/semantics/altIdentifier/url/http://www.cell.com/biophysj/abstract/S0006-3495(10)01364-0
info:eu-repo/semantics/altIdentifier/pmid/PMC3010835
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010835/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
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 13.25334

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