Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency

Autores
Rias, Ezequiel Ignacio; Ouwerkerk, Ingrid; Spitzmaul, Guillermo Federico; Dionisio, Leonardo Raul
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The medial olivocochlear (MOC) system regulates outer hair cell (OHC) excitability. In response to sound overstimulation, MOC activates Ca2+ influx through nicotinic acetylcholine receptors, which stimulates BK and SK2 channels, helping KCNQ4 to remove K+ and restoring membrane potential. KCNQ4 absence results in chronic depolarization, OHC damage, and hearing loss. We evaluated how the absence of KCNQ4 affects the organization and function of the MOC system. Confocal imaging was used to analyze MOC terminal locations on OHC in Kcnq4+/+ (WT) and Kcnq4-/- (KO) mice at 2, 3, 4, and 10 postnatal weeks (W). At 2W, both genotypes have 49% of synaptic contacts in the basal domain and 51% in the lateral domain. In mature animals (≥3W), WT show all terminals in the basal domain, whereas KO kept 8.7%, 16.5%, and 2.9% in the lateral domain at 3, 4, and 10W, respectively. KO mice also had fewer and smaller synaptic contacts per OHC at 4 and 10W compared to WT. Similar results were found in inner hair cells. Using qPCR we demonstrated that, KO mice had a 6-fold decrease in α10 subunit mRNA, with α9 unchanged, and a ~3-fold decrease in BK and SK2 at 4W. By 10W, all tested genes returned to WT levels. Additionally, BK protein was also mislocalized, and some Ca2+-associated proteins showed altered expression at 4W in KO mice. These findings indicate that chronic depolarization alters MOC system development and efferent components expression, leading to functional impairment and hearing loss.
Fil: Rias, Ezequiel Ignacio. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Ouwerkerk, Ingrid. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Spitzmaul, Guillermo Federico. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Dionisio, Leonardo Raul. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Sociedad Argentina de Investigación en Neurociencias Annual Meeting 2024
Buenos Aires
Argentina
Sociedad Argentina de Investigación en Neurociencias
Materia
OHC
EFFERENT SYSTEM
KCNQ4
MATURATION
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:11336/251112
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/251112
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 DeficiencyRias, Ezequiel IgnacioOuwerkerk, IngridSpitzmaul, Guillermo FedericoDionisio, Leonardo RaulOHCEFFERENT SYSTEMKCNQ4MATURATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The medial olivocochlear (MOC) system regulates outer hair cell (OHC) excitability. In response to sound overstimulation, MOC activates Ca2+ influx through nicotinic acetylcholine receptors, which stimulates BK and SK2 channels, helping KCNQ4 to remove K+ and restoring membrane potential. KCNQ4 absence results in chronic depolarization, OHC damage, and hearing loss. We evaluated how the absence of KCNQ4 affects the organization and function of the MOC system. Confocal imaging was used to analyze MOC terminal locations on OHC in Kcnq4+/+ (WT) and Kcnq4-/- (KO) mice at 2, 3, 4, and 10 postnatal weeks (W). At 2W, both genotypes have 49% of synaptic contacts in the basal domain and 51% in the lateral domain. In mature animals (≥3W), WT show all terminals in the basal domain, whereas KO kept 8.7%, 16.5%, and 2.9% in the lateral domain at 3, 4, and 10W, respectively. KO mice also had fewer and smaller synaptic contacts per OHC at 4 and 10W compared to WT. Similar results were found in inner hair cells. Using qPCR we demonstrated that, KO mice had a 6-fold decrease in α10 subunit mRNA, with α9 unchanged, and a ~3-fold decrease in BK and SK2 at 4W. By 10W, all tested genes returned to WT levels. Additionally, BK protein was also mislocalized, and some Ca2+-associated proteins showed altered expression at 4W in KO mice. These findings indicate that chronic depolarization alters MOC system development and efferent components expression, leading to functional impairment and hearing loss.Fil: Rias, Ezequiel Ignacio. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Ouwerkerk, Ingrid. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Spitzmaul, Guillermo Federico. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Dionisio, Leonardo Raul. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaSociedad Argentina de Investigación en Neurociencias Annual Meeting 2024Buenos AiresArgentinaSociedad Argentina de Investigación en NeurocienciasSociedad Argentina de Investigación en Neurociencias2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/251112Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency; Sociedad Argentina de Investigación en Neurociencias Annual Meeting 2024; Buenos Aires; Argentina; 2024; 398-398CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://csan2024.saneurociencias.org.ar/ebook-san2024/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 Técnicas2025-09-03T09:56:37Zoai:ri.conicet.gov.ar:11336/251112instacron: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 09:56:37.443CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency
title Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency
spellingShingle Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency
Rias, Ezequiel Ignacio
OHC
EFFERENT SYSTEM
KCNQ4
MATURATION
title_short Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency
title_full Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency
title_fullStr Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency
title_full_unstemmed Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency
title_sort Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency
dc.creator.none.fl_str_mv Rias, Ezequiel Ignacio
Ouwerkerk, Ingrid
Spitzmaul, Guillermo Federico
Dionisio, Leonardo Raul
author Rias, Ezequiel Ignacio
author_facet Rias, Ezequiel Ignacio
Ouwerkerk, Ingrid
Spitzmaul, Guillermo Federico
Dionisio, Leonardo Raul
author_role author
author2 Ouwerkerk, Ingrid
Spitzmaul, Guillermo Federico
Dionisio, Leonardo Raul
author2_role author
author
author
dc.subject.none.fl_str_mv OHC
EFFERENT SYSTEM
KCNQ4
MATURATION
topic OHC
EFFERENT SYSTEM
KCNQ4
MATURATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The medial olivocochlear (MOC) system regulates outer hair cell (OHC) excitability. In response to sound overstimulation, MOC activates Ca2+ influx through nicotinic acetylcholine receptors, which stimulates BK and SK2 channels, helping KCNQ4 to remove K+ and restoring membrane potential. KCNQ4 absence results in chronic depolarization, OHC damage, and hearing loss. We evaluated how the absence of KCNQ4 affects the organization and function of the MOC system. Confocal imaging was used to analyze MOC terminal locations on OHC in Kcnq4+/+ (WT) and Kcnq4-/- (KO) mice at 2, 3, 4, and 10 postnatal weeks (W). At 2W, both genotypes have 49% of synaptic contacts in the basal domain and 51% in the lateral domain. In mature animals (≥3W), WT show all terminals in the basal domain, whereas KO kept 8.7%, 16.5%, and 2.9% in the lateral domain at 3, 4, and 10W, respectively. KO mice also had fewer and smaller synaptic contacts per OHC at 4 and 10W compared to WT. Similar results were found in inner hair cells. Using qPCR we demonstrated that, KO mice had a 6-fold decrease in α10 subunit mRNA, with α9 unchanged, and a ~3-fold decrease in BK and SK2 at 4W. By 10W, all tested genes returned to WT levels. Additionally, BK protein was also mislocalized, and some Ca2+-associated proteins showed altered expression at 4W in KO mice. These findings indicate that chronic depolarization alters MOC system development and efferent components expression, leading to functional impairment and hearing loss.
Fil: Rias, Ezequiel Ignacio. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Ouwerkerk, Ingrid. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Spitzmaul, Guillermo Federico. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Dionisio, Leonardo Raul. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Sociedad Argentina de Investigación en Neurociencias Annual Meeting 2024
Buenos Aires
Argentina
Sociedad Argentina de Investigación en Neurociencias
description The medial olivocochlear (MOC) system regulates outer hair cell (OHC) excitability. In response to sound overstimulation, MOC activates Ca2+ influx through nicotinic acetylcholine receptors, which stimulates BK and SK2 channels, helping KCNQ4 to remove K+ and restoring membrane potential. KCNQ4 absence results in chronic depolarization, OHC damage, and hearing loss. We evaluated how the absence of KCNQ4 affects the organization and function of the MOC system. Confocal imaging was used to analyze MOC terminal locations on OHC in Kcnq4+/+ (WT) and Kcnq4-/- (KO) mice at 2, 3, 4, and 10 postnatal weeks (W). At 2W, both genotypes have 49% of synaptic contacts in the basal domain and 51% in the lateral domain. In mature animals (≥3W), WT show all terminals in the basal domain, whereas KO kept 8.7%, 16.5%, and 2.9% in the lateral domain at 3, 4, and 10W, respectively. KO mice also had fewer and smaller synaptic contacts per OHC at 4 and 10W compared to WT. Similar results were found in inner hair cells. Using qPCR we demonstrated that, KO mice had a 6-fold decrease in α10 subunit mRNA, with α9 unchanged, and a ~3-fold decrease in BK and SK2 at 4W. By 10W, all tested genes returned to WT levels. Additionally, BK protein was also mislocalized, and some Ca2+-associated proteins showed altered expression at 4W in KO mice. These findings indicate that chronic depolarization alters MOC system development and efferent components expression, leading to functional impairment and hearing loss.
publishDate 2024
dc.date.none.fl_str_mv 2024
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/11336/251112
Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency; Sociedad Argentina de Investigación en Neurociencias Annual Meeting 2024; Buenos Aires; Argentina; 2024; 398-398
CONICET Digital
CONICET
url http://hdl.handle.net/11336/251112
identifier_str_mv Impairment Of The Medial Olivocochlear System Maturation Due To Kcnq4 Deficiency; Sociedad Argentina de Investigación en Neurociencias Annual Meeting 2024; Buenos Aires; Argentina; 2024; 398-398
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://csan2024.saneurociencias.org.ar/ebook-san2024/
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.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)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str 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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