Constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing
Efferent inhibition of cochlear hair cells is mediated by α9α10 nicotinic cholinergic receptors (nAChRs) functionally coupled to calcium-activated, small conductance (SK2) potassium channels. Before the onset of hearing, efferent fibers transiently make functional cholinergic synapses with inner hai...
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| Autores principales: | , , , , , , , , , , |
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| Formato: | Artículo publishedVersion |
| Lenguaje: | Inglés |
| Publicado: |
2009
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| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_15253961_v10_n3_p397_Taranda |
| Aporte de: |
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paperaa:paper_15253961_v10_n3_p397_Taranda |
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| record_format |
dspace |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| language |
Inglés |
| orig_language_str_mv |
eng |
| topic |
Acetylcholine Efferent medial olivocochlear Nicotinic cholinergic receptors SK2 channel Transgenic mice acetylcholine complementary DNA messenger RNA nicotinic acetylcholine receptor alpha10 nicotinic receptor potassium channel SK2 receptor subunit small conductance calcium activated potassium channel unclassified drug acetylcholine cholinergic receptor stimulating agent Chrna10 protein, mouse homeodomain protein Kcnn2 protein, mouse messenger RNA nicotinic receptor Pou4f3 protein, mouse small conductance calcium activated potassium channel transcription factor POU4F3 animal experiment animal tissue article cholinergic synapse Chrna10 gene controlled study down regulation efferent nerve evoked response gene expression genetic transcription hair cell hearing in situ hybridization mouse nonhuman patch clamp potassium current Pou4f3 gene priority journal promoter region receptor gene RNA translation transgene transgenic mouse wild type animal animal model cytology drug effect genetics metabolism physiology Acetylcholine Animals Cholinergic Agents Hair Cells, Auditory, Inner Hearing Homeodomain Proteins Mice Mice, Transgenic Models, Animal Patch-Clamp Techniques Receptors, Nicotinic RNA, Messenger Small-Conductance Calcium-Activated Potassium Channels Transcription Factor Brn-3C |
| spellingShingle |
Acetylcholine Efferent medial olivocochlear Nicotinic cholinergic receptors SK2 channel Transgenic mice acetylcholine complementary DNA messenger RNA nicotinic acetylcholine receptor alpha10 nicotinic receptor potassium channel SK2 receptor subunit small conductance calcium activated potassium channel unclassified drug acetylcholine cholinergic receptor stimulating agent Chrna10 protein, mouse homeodomain protein Kcnn2 protein, mouse messenger RNA nicotinic receptor Pou4f3 protein, mouse small conductance calcium activated potassium channel transcription factor POU4F3 animal experiment animal tissue article cholinergic synapse Chrna10 gene controlled study down regulation efferent nerve evoked response gene expression genetic transcription hair cell hearing in situ hybridization mouse nonhuman patch clamp potassium current Pou4f3 gene priority journal promoter region receptor gene RNA translation transgene transgenic mouse wild type animal animal model cytology drug effect genetics metabolism physiology Acetylcholine Animals Cholinergic Agents Hair Cells, Auditory, Inner Hearing Homeodomain Proteins Mice Mice, Transgenic Models, Animal Patch-Clamp Techniques Receptors, Nicotinic RNA, Messenger Small-Conductance Calcium-Activated Potassium Channels Transcription Factor Brn-3C Taranda, J. Ballestero, J.A. Hiel, H. De Souza, F.S.J. Wedemeyer, C. Gómez-Casati, M.E. Lipovsek, M. Vetter, D.E. Fuchs, P.A. Katz, E. Elgoyhen, A.B. Constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing |
| topic_facet |
Acetylcholine Efferent medial olivocochlear Nicotinic cholinergic receptors SK2 channel Transgenic mice acetylcholine complementary DNA messenger RNA nicotinic acetylcholine receptor alpha10 nicotinic receptor potassium channel SK2 receptor subunit small conductance calcium activated potassium channel unclassified drug acetylcholine cholinergic receptor stimulating agent Chrna10 protein, mouse homeodomain protein Kcnn2 protein, mouse messenger RNA nicotinic receptor Pou4f3 protein, mouse small conductance calcium activated potassium channel transcription factor POU4F3 animal experiment animal tissue article cholinergic synapse Chrna10 gene controlled study down regulation efferent nerve evoked response gene expression genetic transcription hair cell hearing in situ hybridization mouse nonhuman patch clamp potassium current Pou4f3 gene priority journal promoter region receptor gene RNA translation transgene transgenic mouse wild type animal animal model cytology drug effect genetics metabolism physiology Acetylcholine Animals Cholinergic Agents Hair Cells, Auditory, Inner Hearing Homeodomain Proteins Mice Mice, Transgenic Models, Animal Patch-Clamp Techniques Receptors, Nicotinic RNA, Messenger Small-Conductance Calcium-Activated Potassium Channels Transcription Factor Brn-3C |
| description |
Efferent inhibition of cochlear hair cells is mediated by α9α10 nicotinic cholinergic receptors (nAChRs) functionally coupled to calcium-activated, small conductance (SK2) potassium channels. Before the onset of hearing, efferent fibers transiently make functional cholinergic synapses with inner hair cells (IHCs). The retraction of these fibers after the onset of hearing correlates with the cessation of transcription of the Chrna10 (but not the Chrna9) gene in IHCs. To further analyze this developmental change, we generated a transgenic mice whose IHCs constitutively express α10 into adulthood by expressing the α10 cDNA under the control of the Pou4f3 gene promoter. In situ hybridization showed that the α10 mRNA is expressed in IHCs of 8-week-old transgenic mice, but not in wild-type mice. Moreover, this mRNA is translated into a functional protein, since IHCs from P8-P10 α10 transgenic mice backcrossed to a Chrna10 -/- background (whose IHCs have no cholinergic function) displayed normal synaptic and acetylcholine (ACh)-evoked currents in patch-clamp recordings. Thus, the α10 transgene restored nAChR function. However, in the α10 transgenic mice, no synaptic or ACh-evoked currents were observed in P16-18 IHCs, indicating developmental down-regulation of functional nAChRs after the onset of hearing, as normally observed in wild-type mice. The lack of functional ACh currents correlated with the lack of SK2 currents. These results indicate that multiple features of the efferent postsynaptic complex to IHCs, in addition to the nAChR subunits, are down-regulated in synchrony after the onset of hearing, leading to lack of responses to ACh. © 2009 Association for Research in Otolaryngology. |
| format |
Artículo Artículo publishedVersion |
| author |
Taranda, J. Ballestero, J.A. Hiel, H. De Souza, F.S.J. Wedemeyer, C. Gómez-Casati, M.E. Lipovsek, M. Vetter, D.E. Fuchs, P.A. Katz, E. Elgoyhen, A.B. |
| author_facet |
Taranda, J. Ballestero, J.A. Hiel, H. De Souza, F.S.J. Wedemeyer, C. Gómez-Casati, M.E. Lipovsek, M. Vetter, D.E. Fuchs, P.A. Katz, E. Elgoyhen, A.B. |
| author_sort |
Taranda, J. |
| title |
Constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing |
| title_short |
Constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing |
| title_full |
Constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing |
| title_fullStr |
Constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing |
| title_full_unstemmed |
Constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing |
| title_sort |
constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing |
| publishDate |
2009 |
| url |
http://hdl.handle.net/20.500.12110/paper_15253961_v10_n3_p397_Taranda |
| work_keys_str_mv |
AT tarandaj constitutiveexpressionofthea10nicotinicacetylcholinereceptorsubunitfailstomaintaincholinergicresponsesininnerhaircellsaftertheonsetofhearing AT ballesteroja constitutiveexpressionofthea10nicotinicacetylcholinereceptorsubunitfailstomaintaincholinergicresponsesininnerhaircellsaftertheonsetofhearing AT hielh constitutiveexpressionofthea10nicotinicacetylcholinereceptorsubunitfailstomaintaincholinergicresponsesininnerhaircellsaftertheonsetofhearing AT desouzafsj constitutiveexpressionofthea10nicotinicacetylcholinereceptorsubunitfailstomaintaincholinergicresponsesininnerhaircellsaftertheonsetofhearing AT wedemeyerc constitutiveexpressionofthea10nicotinicacetylcholinereceptorsubunitfailstomaintaincholinergicresponsesininnerhaircellsaftertheonsetofhearing AT gomezcasatime constitutiveexpressionofthea10nicotinicacetylcholinereceptorsubunitfailstomaintaincholinergicresponsesininnerhaircellsaftertheonsetofhearing AT lipovsekm constitutiveexpressionofthea10nicotinicacetylcholinereceptorsubunitfailstomaintaincholinergicresponsesininnerhaircellsaftertheonsetofhearing AT vetterde constitutiveexpressionofthea10nicotinicacetylcholinereceptorsubunitfailstomaintaincholinergicresponsesininnerhaircellsaftertheonsetofhearing AT fuchspa constitutiveexpressionofthea10nicotinicacetylcholinereceptorsubunitfailstomaintaincholinergicresponsesininnerhaircellsaftertheonsetofhearing AT katze constitutiveexpressionofthea10nicotinicacetylcholinereceptorsubunitfailstomaintaincholinergicresponsesininnerhaircellsaftertheonsetofhearing AT elgoyhenab constitutiveexpressionofthea10nicotinicacetylcholinereceptorsubunitfailstomaintaincholinergicresponsesininnerhaircellsaftertheonsetofhearing |
| _version_ |
1769810245481136128 |
| spelling |
paperaa:paper_15253961_v10_n3_p397_Taranda2023-06-12T16:50:36Z Constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing JARO J. Assoc. Res. Otolaryngol. 2009;10(3):397-406 Taranda, J. Ballestero, J.A. Hiel, H. De Souza, F.S.J. Wedemeyer, C. Gómez-Casati, M.E. Lipovsek, M. Vetter, D.E. Fuchs, P.A. Katz, E. Elgoyhen, A.B. Acetylcholine Efferent medial olivocochlear Nicotinic cholinergic receptors SK2 channel Transgenic mice acetylcholine complementary DNA messenger RNA nicotinic acetylcholine receptor alpha10 nicotinic receptor potassium channel SK2 receptor subunit small conductance calcium activated potassium channel unclassified drug acetylcholine cholinergic receptor stimulating agent Chrna10 protein, mouse homeodomain protein Kcnn2 protein, mouse messenger RNA nicotinic receptor Pou4f3 protein, mouse small conductance calcium activated potassium channel transcription factor POU4F3 animal experiment animal tissue article cholinergic synapse Chrna10 gene controlled study down regulation efferent nerve evoked response gene expression genetic transcription hair cell hearing in situ hybridization mouse nonhuman patch clamp potassium current Pou4f3 gene priority journal promoter region receptor gene RNA translation transgene transgenic mouse wild type animal animal model cytology drug effect genetics metabolism physiology Acetylcholine Animals Cholinergic Agents Hair Cells, Auditory, Inner Hearing Homeodomain Proteins Mice Mice, Transgenic Models, Animal Patch-Clamp Techniques Receptors, Nicotinic RNA, Messenger Small-Conductance Calcium-Activated Potassium Channels Transcription Factor Brn-3C Efferent inhibition of cochlear hair cells is mediated by α9α10 nicotinic cholinergic receptors (nAChRs) functionally coupled to calcium-activated, small conductance (SK2) potassium channels. Before the onset of hearing, efferent fibers transiently make functional cholinergic synapses with inner hair cells (IHCs). The retraction of these fibers after the onset of hearing correlates with the cessation of transcription of the Chrna10 (but not the Chrna9) gene in IHCs. To further analyze this developmental change, we generated a transgenic mice whose IHCs constitutively express α10 into adulthood by expressing the α10 cDNA under the control of the Pou4f3 gene promoter. In situ hybridization showed that the α10 mRNA is expressed in IHCs of 8-week-old transgenic mice, but not in wild-type mice. Moreover, this mRNA is translated into a functional protein, since IHCs from P8-P10 α10 transgenic mice backcrossed to a Chrna10 -/- background (whose IHCs have no cholinergic function) displayed normal synaptic and acetylcholine (ACh)-evoked currents in patch-clamp recordings. Thus, the α10 transgene restored nAChR function. However, in the α10 transgenic mice, no synaptic or ACh-evoked currents were observed in P16-18 IHCs, indicating developmental down-regulation of functional nAChRs after the onset of hearing, as normally observed in wild-type mice. The lack of functional ACh currents correlated with the lack of SK2 currents. These results indicate that multiple features of the efferent postsynaptic complex to IHCs, in addition to the nAChR subunits, are down-regulated in synchrony after the onset of hearing, leading to lack of responses to ACh. © 2009 Association for Research in Otolaryngology. Fil:Taranda, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ballestero, J.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Wedemeyer, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gómez-Casati, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Lipovsek, M. 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. 2009 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15253961_v10_n3_p397_Taranda |