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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/246241
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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 Técnicas2025-09-03T09:43:29Zoai: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:34982025-09-03 09:43:29.785CONICET 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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.13397 |