Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds

Autores
Nielsen, Beatriz Elizabeth; Andersen, Natalia Denise; Corradi, Jeremias; Bouzat, Cecilia Beatriz
Año de publicación
2015
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Alpha 7 nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system, mainly in hippocampus and cortex, and are implicated in several neurological disorders such as Alzheimer´s disease and schizophrenia. Enhancement of α7 nAChR activity by positive allosteric modulators (PAMs) is a promising therapeutic strategy to improve cognitive deficits. PAM activity has been evaluated mainly at the macroscopic level, and PAMs have been classified as type I, which increase α7 currents, and type II, which cause also a profound decrease in desensitization and/or reactivate desensitized receptors. In addition, most in vitro studies have been performed at room temperature whereas preclinical studies and clinical use require physiological temperatures. To cover these limitations we evaluated potentiation of human α7 at the single-channel level. Our results revealed that both types of PAMs enhance open-channel lifetime and produce activation episodes of successive opening events. By analyzing their activities at a physiological temperature, we found that potentiation decreases with respect to room temperature. However, both PAM types show different sensitivity to temperature, suggesting distinct mechanisms by which they induce sustained activation. Overall, temperature dependence analysis emerges as a key requisite during evaluation of potential clinical applications of PAMs.
Fil: Nielsen, Beatriz Elizabeth. 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: 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: 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
XXX Annual Meeting Sociedad Argentina de Neurociencias - International Society for Neurochemistry Small Conference and Course
Mar del Plata
Argentina
Sociedad Argentina de Neurociencias
International Society for Neurochemistry
Materia
CYS-LOOP
PATCH-CLAMP
TEMPERATURE
MODULATION
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:11336/246241
Acceder
id CONICETDig_bc7579b8af5c009621ff10d00fb917f4
oai_identifier_str oai:ri.conicet.gov.ar:11336/246241
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic CompoundsNielsen, Beatriz ElizabethAndersen, Natalia DeniseCorradi, JeremiasBouzat, Cecilia BeatrizCYS-LOOPPATCH-CLAMPTEMPERATUREMODULATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Alpha 7 nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system, mainly in hippocampus and cortex, and are implicated in several neurological disorders such as Alzheimer´s disease and schizophrenia. Enhancement of α7 nAChR activity by positive allosteric modulators (PAMs) is a promising therapeutic strategy to improve cognitive deficits. PAM activity has been evaluated mainly at the macroscopic level, and PAMs have been classified as type I, which increase α7 currents, and type II, which cause also a profound decrease in desensitization and/or reactivate desensitized receptors. In addition, most in vitro studies have been performed at room temperature whereas preclinical studies and clinical use require physiological temperatures. To cover these limitations we evaluated potentiation of human α7 at the single-channel level. Our results revealed that both types of PAMs enhance open-channel lifetime and produce activation episodes of successive opening events. By analyzing their activities at a physiological temperature, we found that potentiation decreases with respect to room temperature. However, both PAM types show different sensitivity to temperature, suggesting distinct mechanisms by which they induce sustained activation. Overall, temperature dependence analysis emerges as a key requisite during evaluation of potential clinical applications of PAMs.Fil: Nielsen, Beatriz Elizabeth. 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: 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: 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; ArgentinaXXX Annual Meeting Sociedad Argentina de Neurociencias - International Society for Neurochemistry Small Conference and CourseMar del PlataArgentinaSociedad Argentina de NeurocienciasInternational Society for NeurochemistrySociedad Argentina de Neurociencias2015info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/246241Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds; XXX Annual Meeting Sociedad Argentina de Neurociencias - International Society for Neurochemistry Small Conference and Course; Mar del Plata; Argentina; 2015; 300-300CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/congresos-san-2/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:32:43Zoai:ri.conicet.gov.ar:11336/246241instacron: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 09:32:44.028CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds
title Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds
spellingShingle Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds
Nielsen, Beatriz Elizabeth
CYS-LOOP
PATCH-CLAMP
TEMPERATURE
MODULATION
title_short Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds
title_full Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds
title_fullStr Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds
title_full_unstemmed Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds
title_sort Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds
dc.creator.none.fl_str_mv Nielsen, Beatriz Elizabeth
Andersen, Natalia Denise
Corradi, Jeremias
Bouzat, Cecilia Beatriz
author Nielsen, Beatriz Elizabeth
author_facet Nielsen, Beatriz Elizabeth
Andersen, Natalia Denise
Corradi, Jeremias
Bouzat, Cecilia Beatriz
author_role author
author2 Andersen, Natalia Denise
Corradi, Jeremias
Bouzat, Cecilia Beatriz
author2_role author
author
author
dc.subject.none.fl_str_mv CYS-LOOP
PATCH-CLAMP
TEMPERATURE
MODULATION
topic CYS-LOOP
PATCH-CLAMP
TEMPERATURE
MODULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Alpha 7 nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system, mainly in hippocampus and cortex, and are implicated in several neurological disorders such as Alzheimer´s disease and schizophrenia. Enhancement of α7 nAChR activity by positive allosteric modulators (PAMs) is a promising therapeutic strategy to improve cognitive deficits. PAM activity has been evaluated mainly at the macroscopic level, and PAMs have been classified as type I, which increase α7 currents, and type II, which cause also a profound decrease in desensitization and/or reactivate desensitized receptors. In addition, most in vitro studies have been performed at room temperature whereas preclinical studies and clinical use require physiological temperatures. To cover these limitations we evaluated potentiation of human α7 at the single-channel level. Our results revealed that both types of PAMs enhance open-channel lifetime and produce activation episodes of successive opening events. By analyzing their activities at a physiological temperature, we found that potentiation decreases with respect to room temperature. However, both PAM types show different sensitivity to temperature, suggesting distinct mechanisms by which they induce sustained activation. Overall, temperature dependence analysis emerges as a key requisite during evaluation of potential clinical applications of PAMs.
Fil: Nielsen, Beatriz Elizabeth. 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: 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: 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
XXX Annual Meeting Sociedad Argentina de Neurociencias - International Society for Neurochemistry Small Conference and Course
Mar del Plata
Argentina
Sociedad Argentina de Neurociencias
International Society for Neurochemistry
description Alpha 7 nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system, mainly in hippocampus and cortex, and are implicated in several neurological disorders such as Alzheimer´s disease and schizophrenia. Enhancement of α7 nAChR activity by positive allosteric modulators (PAMs) is a promising therapeutic strategy to improve cognitive deficits. PAM activity has been evaluated mainly at the macroscopic level, and PAMs have been classified as type I, which increase α7 currents, and type II, which cause also a profound decrease in desensitization and/or reactivate desensitized receptors. In addition, most in vitro studies have been performed at room temperature whereas preclinical studies and clinical use require physiological temperatures. To cover these limitations we evaluated potentiation of human α7 at the single-channel level. Our results revealed that both types of PAMs enhance open-channel lifetime and produce activation episodes of successive opening events. By analyzing their activities at a physiological temperature, we found that potentiation decreases with respect to room temperature. However, both PAM types show different sensitivity to temperature, suggesting distinct mechanisms by which they induce sustained activation. Overall, temperature dependence analysis emerges as a key requisite during evaluation of potential clinical applications of PAMs.
publishDate 2015
dc.date.none.fl_str_mv 2015
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/11336/246241
Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds; XXX Annual Meeting Sociedad Argentina de Neurociencias - International Society for Neurochemistry Small Conference and Course; Mar del Plata; Argentina; 2015; 300-300
CONICET Digital
CONICET
url http://hdl.handle.net/11336/246241
identifier_str_mv Temperature Dependence of the Enhancement of a7 Nicotinic Receptor Activity by Potential Therapeutic Compounds; XXX Annual Meeting Sociedad Argentina de Neurociencias - International Society for Neurochemistry Small Conference and Course; Mar del Plata; Argentina; 2015; 300-300
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Neurociencias
publisher.none.fl_str_mv Sociedad Argentina de Neurociencias
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
_version_ 1844613000188657664
score 13.070432

Publicaciones similares