Synaptic contributions to cochlear outer hair cell Ca2+ dynamics

Autores
Moglie, Marcelo Javier; Wengier, Diego Leonardo; Elgoyhen, Ana Belen; Goutman, Juan Diego
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
For normal cochlear function, outer hair cells (OHCs) require a precise control of intracellular Ca21 levels. In the absence of regulatory elements such as proteinaceous buffers or extrusion pumps, OHCs degenerate, leading to profound hearing impairment. Influx of Ca21 occurs both at the stereocilia tips and the basolateral membrane. In this latter compartment, two different origins for Ca21 influx have been poorly explored: voltage-gated L-type Ca21 channels (VGCCs) at synapses with Type II afferent neurons, and a9a10 cholinergic nicotinic receptors at synapses with medio-olivochlear complex (MOC) neurons. Using functional imaging in mouse OHCs, we dissected Ca21 influx individually through each of these sources, either by applying step depolarizations to activate VGCC, or stimulating MOC axons. Ca21 ions originated in MOC synapses, but not by VGCC activation, was confined by Ca21-ATPases most likely present in nearby synaptic cisterns. Although Ca21 currents in OHCs are small, VGCC Ca21 signals were comparable in size to those elicited by a9a10 receptors, and were potentiated by ryanodine receptors (RyRs). In contrast, no evidence of potentiation by RyRs was found for MOC Ca21 signals over a wide range of presynaptic stimulation strengths. Our study shows that despite the fact that these two Ca21 entry sites are closely positioned, they differ in their regulation by intracellular cisterns and/or organelles, suggesting the existence of well-tuned mechanisms to separate the two different OHC synaptic functions.
Fil: Moglie, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Wengier, Diego Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Materia
CALCIUM
CISTERN
OUTER HAIR CELL
SYNAPSES
VOLTAGE-GATED CA2+ CHANNELS
Α9Α10
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:11336/163444

id CONICETDig_758e074038ac6492837af250abee4155
oai_identifier_str oai:ri.conicet.gov.ar:11336/163444
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synaptic contributions to cochlear outer hair cell Ca2+ dynamicsMoglie, Marcelo JavierWengier, Diego LeonardoElgoyhen, Ana BelenGoutman, Juan DiegoCALCIUMCISTERNOUTER HAIR CELLSYNAPSESVOLTAGE-GATED CA2+ CHANNELSΑ9Α10https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1For normal cochlear function, outer hair cells (OHCs) require a precise control of intracellular Ca21 levels. In the absence of regulatory elements such as proteinaceous buffers or extrusion pumps, OHCs degenerate, leading to profound hearing impairment. Influx of Ca21 occurs both at the stereocilia tips and the basolateral membrane. In this latter compartment, two different origins for Ca21 influx have been poorly explored: voltage-gated L-type Ca21 channels (VGCCs) at synapses with Type II afferent neurons, and a9a10 cholinergic nicotinic receptors at synapses with medio-olivochlear complex (MOC) neurons. Using functional imaging in mouse OHCs, we dissected Ca21 influx individually through each of these sources, either by applying step depolarizations to activate VGCC, or stimulating MOC axons. Ca21 ions originated in MOC synapses, but not by VGCC activation, was confined by Ca21-ATPases most likely present in nearby synaptic cisterns. Although Ca21 currents in OHCs are small, VGCC Ca21 signals were comparable in size to those elicited by a9a10 receptors, and were potentiated by ryanodine receptors (RyRs). In contrast, no evidence of potentiation by RyRs was found for MOC Ca21 signals over a wide range of presynaptic stimulation strengths. Our study shows that despite the fact that these two Ca21 entry sites are closely positioned, they differ in their regulation by intracellular cisterns and/or organelles, suggesting the existence of well-tuned mechanisms to separate the two different OHC synaptic functions.Fil: Moglie, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Wengier, Diego Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaSociety for Neuroscience2021-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/163444Moglie, Marcelo Javier; Wengier, Diego Leonardo; Elgoyhen, Ana Belen; Goutman, Juan Diego; Synaptic contributions to cochlear outer hair cell Ca2+ dynamics; Society for Neuroscience; Journal of Neuroscience; 41; 32; 8-2021; 6812-68210270-6474CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.3008-20.2021info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/41/32/6812info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:02Zoai:ri.conicet.gov.ar:11336/163444instacron: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 10:10:03.066CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synaptic contributions to cochlear outer hair cell Ca2+ dynamics
title Synaptic contributions to cochlear outer hair cell Ca2+ dynamics
spellingShingle Synaptic contributions to cochlear outer hair cell Ca2+ dynamics
Moglie, Marcelo Javier
CALCIUM
CISTERN
OUTER HAIR CELL
SYNAPSES
VOLTAGE-GATED CA2+ CHANNELS
Α9Α10
title_short Synaptic contributions to cochlear outer hair cell Ca2+ dynamics
title_full Synaptic contributions to cochlear outer hair cell Ca2+ dynamics
title_fullStr Synaptic contributions to cochlear outer hair cell Ca2+ dynamics
title_full_unstemmed Synaptic contributions to cochlear outer hair cell Ca2+ dynamics
title_sort Synaptic contributions to cochlear outer hair cell Ca2+ dynamics
dc.creator.none.fl_str_mv Moglie, Marcelo Javier
Wengier, Diego Leonardo
Elgoyhen, Ana Belen
Goutman, Juan Diego
author Moglie, Marcelo Javier
author_facet Moglie, Marcelo Javier
Wengier, Diego Leonardo
Elgoyhen, Ana Belen
Goutman, Juan Diego
author_role author
author2 Wengier, Diego Leonardo
Elgoyhen, Ana Belen
Goutman, Juan Diego
author2_role author
author
author
dc.subject.none.fl_str_mv CALCIUM
CISTERN
OUTER HAIR CELL
SYNAPSES
VOLTAGE-GATED CA2+ CHANNELS
Α9Α10
topic CALCIUM
CISTERN
OUTER HAIR CELL
SYNAPSES
VOLTAGE-GATED CA2+ CHANNELS
Α9Α10
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv For normal cochlear function, outer hair cells (OHCs) require a precise control of intracellular Ca21 levels. In the absence of regulatory elements such as proteinaceous buffers or extrusion pumps, OHCs degenerate, leading to profound hearing impairment. Influx of Ca21 occurs both at the stereocilia tips and the basolateral membrane. In this latter compartment, two different origins for Ca21 influx have been poorly explored: voltage-gated L-type Ca21 channels (VGCCs) at synapses with Type II afferent neurons, and a9a10 cholinergic nicotinic receptors at synapses with medio-olivochlear complex (MOC) neurons. Using functional imaging in mouse OHCs, we dissected Ca21 influx individually through each of these sources, either by applying step depolarizations to activate VGCC, or stimulating MOC axons. Ca21 ions originated in MOC synapses, but not by VGCC activation, was confined by Ca21-ATPases most likely present in nearby synaptic cisterns. Although Ca21 currents in OHCs are small, VGCC Ca21 signals were comparable in size to those elicited by a9a10 receptors, and were potentiated by ryanodine receptors (RyRs). In contrast, no evidence of potentiation by RyRs was found for MOC Ca21 signals over a wide range of presynaptic stimulation strengths. Our study shows that despite the fact that these two Ca21 entry sites are closely positioned, they differ in their regulation by intracellular cisterns and/or organelles, suggesting the existence of well-tuned mechanisms to separate the two different OHC synaptic functions.
Fil: Moglie, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Wengier, Diego Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
description For normal cochlear function, outer hair cells (OHCs) require a precise control of intracellular Ca21 levels. In the absence of regulatory elements such as proteinaceous buffers or extrusion pumps, OHCs degenerate, leading to profound hearing impairment. Influx of Ca21 occurs both at the stereocilia tips and the basolateral membrane. In this latter compartment, two different origins for Ca21 influx have been poorly explored: voltage-gated L-type Ca21 channels (VGCCs) at synapses with Type II afferent neurons, and a9a10 cholinergic nicotinic receptors at synapses with medio-olivochlear complex (MOC) neurons. Using functional imaging in mouse OHCs, we dissected Ca21 influx individually through each of these sources, either by applying step depolarizations to activate VGCC, or stimulating MOC axons. Ca21 ions originated in MOC synapses, but not by VGCC activation, was confined by Ca21-ATPases most likely present in nearby synaptic cisterns. Although Ca21 currents in OHCs are small, VGCC Ca21 signals were comparable in size to those elicited by a9a10 receptors, and were potentiated by ryanodine receptors (RyRs). In contrast, no evidence of potentiation by RyRs was found for MOC Ca21 signals over a wide range of presynaptic stimulation strengths. Our study shows that despite the fact that these two Ca21 entry sites are closely positioned, they differ in their regulation by intracellular cisterns and/or organelles, suggesting the existence of well-tuned mechanisms to separate the two different OHC synaptic functions.
publishDate 2021
dc.date.none.fl_str_mv 2021-08
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/11336/163444
Moglie, Marcelo Javier; Wengier, Diego Leonardo; Elgoyhen, Ana Belen; Goutman, Juan Diego; Synaptic contributions to cochlear outer hair cell Ca2+ dynamics; Society for Neuroscience; Journal of Neuroscience; 41; 32; 8-2021; 6812-6821
0270-6474
CONICET Digital
CONICET
url http://hdl.handle.net/11336/163444
identifier_str_mv Moglie, Marcelo Javier; Wengier, Diego Leonardo; Elgoyhen, Ana Belen; Goutman, Juan Diego; Synaptic contributions to cochlear outer hair cell Ca2+ dynamics; Society for Neuroscience; Journal of Neuroscience; 41; 32; 8-2021; 6812-6821
0270-6474
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.3008-20.2021
info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/41/32/6812
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.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
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_ 1842270104346165248
score 13.13397