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
- Institución
- Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
- OAI Identificador
- paperaa:paper_15253961_v8_n4_p474_ZorrillaDeSanMartin
Ver los metadatos del registro completo
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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) |
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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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