Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cells

Autores
Zorrilla De San Martín, J.; Ballestero, J.; Katz, E.; Elgoyhen, A.B.; Fuchs, P.A.
Año de publicación
2007
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The efferent synaptic specialization of hair cells includes a near-membrane synaptic cistern, whose presence suggests a role for internal calcium stores in cholinergic inhibition. Calcium release channels from internal stores include 'ryanodine receptors', whose participation is usually demonstrated by sensitivity to the eponymous plant alkaloid, ryanodine. However, use of this and other store-active compounds on hair cells could be confounded by the unusual pharmacology of the α9α10-containing hair cell nicotinic cholinergic receptor (nAChR), which has been shown to be antagonized by a broad spectrum of compounds. Surprisingly, we found that ryanodine, rather than antagonizing, is a positive modulator of the α9α10 nAChR expressed in Xenopus oocytes, the first such compound to be found. The effect of ryanodine was to increase the apparent affinity and efficacy for acetylcholine (ACh). Correspondingly, ACh-evoked currents through the isolated cholinergic receptors of inner hair cells in excised mouse cochleas were approximately doubled by 200 μM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This unusual positive modulation was not unique to the mammalian receptor. The response to ACh of chicken 'short' hair cells likewise was enhanced in the presence of 100 μM ryanodine. This facilitatory effect on current through the AChR could enhance brief (∼1 s) activation of associated calcium-dependent K+ (SK) channels in both chicken short hair cells and rat outer hair cells. This novel effect of ryanodine provides new opportunities for the design of compounds that potentiate α9α10- mediated responses and for potential inner ear therapeutics based on this interaction. © 2007 Association for Research in Otolaryngology.
Fil:Zorrilla De San Martín, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Ballestero, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fuente
JARO J. Assoc. Res. Otolaryngol. 2007;8(4):474-483
Materia
α9α10 receptors
Acetylcholine
Efferent system
Ion channels
Nicotinic receptors
Ryanodine
acetylcholine
alkaloid
calcium
calcium channel
cholinergic receptor
nicotinic acetylcholine receptor alpha10
nicotinic acetylcholine receptor alpha9
potassium channel
ryanodine
unclassified drug
animal cell
article
calcium transport
cell specificity
channel gating
cholinergic system
cochlea
controlled study
facilitation
gene expression
hair cell
membrane current
mouse
nerve cell plasticity
nonhuman
oocyte
priority journal
receptor affinity
Xenopus
Xenopus laevis
Acetylcholine
Animals
Chickens
Dose-Response Relationship, Drug
Hair Cells, Auditory
Ion Channel Gating
Mice
Potassium Channels, Calcium-Activated
Protein Subunits
Rats
Receptors, Cholinergic
Receptors, Nicotinic
Ryanodine
Xenopus laevis
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/2.5/ar
Repositorio
Biblioteca Digital (UBA-FCEN)
Institución
Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
OAI Identificador
paperaa:paper_15253961_v8_n4_p474_ZorrillaDeSanMartin

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oai_identifier_str paperaa:paper_15253961_v8_n4_p474_ZorrillaDeSanMartin
network_acronym_str BDUBAFCEN
repository_id_str 1896
network_name_str Biblioteca Digital (UBA-FCEN)
spelling Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cellsZorrilla De San Martín, J.Ballestero, J.Katz, E.Elgoyhen, A.B.Fuchs, P.A.α9α10 receptorsAcetylcholineEfferent systemIon channelsNicotinic receptorsRyanodineacetylcholinealkaloidcalciumcalcium channelcholinergic receptornicotinic acetylcholine receptor alpha10nicotinic acetylcholine receptor alpha9potassium channelryanodineunclassified druganimal cellarticlecalcium transportcell specificitychannel gatingcholinergic systemcochleacontrolled studyfacilitationgene expressionhair cellmembrane currentmousenerve cell plasticitynonhumanoocytepriority journalreceptor affinityXenopusXenopus laevisAcetylcholineAnimalsChickensDose-Response Relationship, DrugHair Cells, AuditoryIon Channel GatingMicePotassium Channels, Calcium-ActivatedProtein SubunitsRatsReceptors, CholinergicReceptors, NicotinicRyanodineXenopus laevisThe efferent synaptic specialization of hair cells includes a near-membrane synaptic cistern, whose presence suggests a role for internal calcium stores in cholinergic inhibition. Calcium release channels from internal stores include 'ryanodine receptors', whose participation is usually demonstrated by sensitivity to the eponymous plant alkaloid, ryanodine. However, use of this and other store-active compounds on hair cells could be confounded by the unusual pharmacology of the α9α10-containing hair cell nicotinic cholinergic receptor (nAChR), which has been shown to be antagonized by a broad spectrum of compounds. Surprisingly, we found that ryanodine, rather than antagonizing, is a positive modulator of the α9α10 nAChR expressed in Xenopus oocytes, the first such compound to be found. The effect of ryanodine was to increase the apparent affinity and efficacy for acetylcholine (ACh). Correspondingly, ACh-evoked currents through the isolated cholinergic receptors of inner hair cells in excised mouse cochleas were approximately doubled by 200 μM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This unusual positive modulation was not unique to the mammalian receptor. The response to ACh of chicken 'short' hair cells likewise was enhanced in the presence of 100 μM ryanodine. This facilitatory effect on current through the AChR could enhance brief (∼1 s) activation of associated calcium-dependent K+ (SK) channels in both chicken short hair cells and rat outer hair cells. This novel effect of ryanodine provides new opportunities for the design of compounds that potentiate α9α10- mediated responses and for potential inner ear therapeutics based on this interaction. © 2007 Association for Research in Otolaryngology.Fil:Zorrilla De San Martín, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Ballestero, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.2007info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12110/paper_15253961_v8_n4_p474_ZorrillaDeSanMartinJARO J. Assoc. Res. Otolaryngol. 2007;8(4):474-483reponame:Biblioteca Digital (UBA-FCEN)instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesinstacron:UBA-FCENenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/2.5/ar2025-09-29T13:42:58Zpaperaa:paper_15253961_v8_n4_p474_ZorrillaDeSanMartinInstitucionalhttps://digital.bl.fcen.uba.ar/Universidad públicaNo correspondehttps://digital.bl.fcen.uba.ar/cgi-bin/oaiserver.cgiana@bl.fcen.uba.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:18962025-09-29 13:42:59.325Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesfalse
dc.title.none.fl_str_mv Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cells
title Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cells
spellingShingle Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cells
Zorrilla De San Martín, J.
α9α10 receptors
Acetylcholine
Efferent system
Ion channels
Nicotinic receptors
Ryanodine
acetylcholine
alkaloid
calcium
calcium channel
cholinergic receptor
nicotinic acetylcholine receptor alpha10
nicotinic acetylcholine receptor alpha9
potassium channel
ryanodine
unclassified drug
animal cell
article
calcium transport
cell specificity
channel gating
cholinergic system
cochlea
controlled study
facilitation
gene expression
hair cell
membrane current
mouse
nerve cell plasticity
nonhuman
oocyte
priority journal
receptor affinity
Xenopus
Xenopus laevis
Acetylcholine
Animals
Chickens
Dose-Response Relationship, Drug
Hair Cells, Auditory
Ion Channel Gating
Mice
Potassium Channels, Calcium-Activated
Protein Subunits
Rats
Receptors, Cholinergic
Receptors, Nicotinic
Ryanodine
Xenopus laevis
title_short Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cells
title_full Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cells
title_fullStr Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cells
title_full_unstemmed Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cells
title_sort Ryanodine is a positive modulator of acetylcholine receptor gating in cochlear hair cells
dc.creator.none.fl_str_mv Zorrilla De San Martín, J.
Ballestero, J.
Katz, E.
Elgoyhen, A.B.
Fuchs, P.A.
author Zorrilla De San Martín, J.
author_facet Zorrilla De San Martín, J.
Ballestero, J.
Katz, E.
Elgoyhen, A.B.
Fuchs, P.A.
author_role author
author2 Ballestero, J.
Katz, E.
Elgoyhen, A.B.
Fuchs, P.A.
author2_role author
author
author
author
dc.subject.none.fl_str_mv α9α10 receptors
Acetylcholine
Efferent system
Ion channels
Nicotinic receptors
Ryanodine
acetylcholine
alkaloid
calcium
calcium channel
cholinergic receptor
nicotinic acetylcholine receptor alpha10
nicotinic acetylcholine receptor alpha9
potassium channel
ryanodine
unclassified drug
animal cell
article
calcium transport
cell specificity
channel gating
cholinergic system
cochlea
controlled study
facilitation
gene expression
hair cell
membrane current
mouse
nerve cell plasticity
nonhuman
oocyte
priority journal
receptor affinity
Xenopus
Xenopus laevis
Acetylcholine
Animals
Chickens
Dose-Response Relationship, Drug
Hair Cells, Auditory
Ion Channel Gating
Mice
Potassium Channels, Calcium-Activated
Protein Subunits
Rats
Receptors, Cholinergic
Receptors, Nicotinic
Ryanodine
Xenopus laevis
topic α9α10 receptors
Acetylcholine
Efferent system
Ion channels
Nicotinic receptors
Ryanodine
acetylcholine
alkaloid
calcium
calcium channel
cholinergic receptor
nicotinic acetylcholine receptor alpha10
nicotinic acetylcholine receptor alpha9
potassium channel
ryanodine
unclassified drug
animal cell
article
calcium transport
cell specificity
channel gating
cholinergic system
cochlea
controlled study
facilitation
gene expression
hair cell
membrane current
mouse
nerve cell plasticity
nonhuman
oocyte
priority journal
receptor affinity
Xenopus
Xenopus laevis
Acetylcholine
Animals
Chickens
Dose-Response Relationship, Drug
Hair Cells, Auditory
Ion Channel Gating
Mice
Potassium Channels, Calcium-Activated
Protein Subunits
Rats
Receptors, Cholinergic
Receptors, Nicotinic
Ryanodine
Xenopus laevis
dc.description.none.fl_txt_mv The efferent synaptic specialization of hair cells includes a near-membrane synaptic cistern, whose presence suggests a role for internal calcium stores in cholinergic inhibition. Calcium release channels from internal stores include 'ryanodine receptors', whose participation is usually demonstrated by sensitivity to the eponymous plant alkaloid, ryanodine. However, use of this and other store-active compounds on hair cells could be confounded by the unusual pharmacology of the α9α10-containing hair cell nicotinic cholinergic receptor (nAChR), which has been shown to be antagonized by a broad spectrum of compounds. Surprisingly, we found that ryanodine, rather than antagonizing, is a positive modulator of the α9α10 nAChR expressed in Xenopus oocytes, the first such compound to be found. The effect of ryanodine was to increase the apparent affinity and efficacy for acetylcholine (ACh). Correspondingly, ACh-evoked currents through the isolated cholinergic receptors of inner hair cells in excised mouse cochleas were approximately doubled by 200 μM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This unusual positive modulation was not unique to the mammalian receptor. The response to ACh of chicken 'short' hair cells likewise was enhanced in the presence of 100 μM ryanodine. This facilitatory effect on current through the AChR could enhance brief (∼1 s) activation of associated calcium-dependent K+ (SK) channels in both chicken short hair cells and rat outer hair cells. This novel effect of ryanodine provides new opportunities for the design of compounds that potentiate α9α10- mediated responses and for potential inner ear therapeutics based on this interaction. © 2007 Association for Research in Otolaryngology.
Fil:Zorrilla De San Martín, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Ballestero, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
description The efferent synaptic specialization of hair cells includes a near-membrane synaptic cistern, whose presence suggests a role for internal calcium stores in cholinergic inhibition. Calcium release channels from internal stores include 'ryanodine receptors', whose participation is usually demonstrated by sensitivity to the eponymous plant alkaloid, ryanodine. However, use of this and other store-active compounds on hair cells could be confounded by the unusual pharmacology of the α9α10-containing hair cell nicotinic cholinergic receptor (nAChR), which has been shown to be antagonized by a broad spectrum of compounds. Surprisingly, we found that ryanodine, rather than antagonizing, is a positive modulator of the α9α10 nAChR expressed in Xenopus oocytes, the first such compound to be found. The effect of ryanodine was to increase the apparent affinity and efficacy for acetylcholine (ACh). Correspondingly, ACh-evoked currents through the isolated cholinergic receptors of inner hair cells in excised mouse cochleas were approximately doubled by 200 μM ryanodine, a concentration that inhibits gating of the ryanodine receptor itself. This unusual positive modulation was not unique to the mammalian receptor. The response to ACh of chicken 'short' hair cells likewise was enhanced in the presence of 100 μM ryanodine. This facilitatory effect on current through the AChR could enhance brief (∼1 s) activation of associated calcium-dependent K+ (SK) channels in both chicken short hair cells and rat outer hair cells. This novel effect of ryanodine provides new opportunities for the design of compounds that potentiate α9α10- mediated responses and for potential inner ear therapeutics based on this interaction. © 2007 Association for Research in Otolaryngology.
publishDate 2007
dc.date.none.fl_str_mv 2007
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/20.500.12110/paper_15253961_v8_n4_p474_ZorrillaDeSanMartin
url http://hdl.handle.net/20.500.12110/paper_15253961_v8_n4_p474_ZorrillaDeSanMartin
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/2.5/ar
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/2.5/ar
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv JARO J. Assoc. Res. Otolaryngol. 2007;8(4):474-483
reponame:Biblioteca Digital (UBA-FCEN)
instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron:UBA-FCEN
reponame_str Biblioteca Digital (UBA-FCEN)
collection Biblioteca Digital (UBA-FCEN)
instname_str Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron_str UBA-FCEN
institution UBA-FCEN
repository.name.fl_str_mv Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
repository.mail.fl_str_mv ana@bl.fcen.uba.ar
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