Abstract:
Although homomeric channels assembled from the α9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both α9 and α10 subunits. To gain insight into α10 subunit function in vivo, we examined olivocochlear innervation and function in α10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in α10 +/+ and α10+/- mice, with no detectable responses to ACh in α10+/+ mice. In contrast, a proportion of α10-/- outer hair cells showed small ACh-evoked currents. In α10-/- mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual α9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, α10-/- mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. Our results demonstrate that α9-/- and α10-/- mice have overlapping but nonidentical phenotypes. Moreover, α10 nAChR subunits are required for normal olivocochlear activity because α9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in α10-/- mutant mice. © 2007 by The National Academy of Sciences of the USA.
Registro:
Documento: |
Artículo
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Título: | The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system |
Autor: | Vetter, D.E.; Katz, E.; Maison, S.F.; Taranda, J.N.; Turcan, S.; Ballestero, J.; Liberman, M.C.; Elgoyhen, A.B.N.; Boulter, J. |
Filiación: | Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, United States Department of Biomedical Engineering, Tufts University, Boston, MA 02111, United States Instituto de Investigaciones en Ingenieria Genetica Y Biologi a Molecular (INGEBI), Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET), Buenos Aires 1428, Argentina Departamento de Fisiología, Biologí a Molecular Y Celular, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, United States Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, United States Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires 1121, Argentina Department of Psychiatry and Biobehavioral Sciences, Brain Research and Molecular Biology Institutes, University of California, Los Angeles, CA 90024, United States Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Avenue, Boston, MA 02111, United States
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Palabras clave: | Cochlea; Electrophysiology; Inner hair cells; Outer hair cells; nicotinic receptor; nicotinic receptor alpha10; receptor subunit; unclassified drug; Chrna10 protein, mouse; Chrna9 protein, mouse; nicotinic receptor; animal cell; animal experiment; article; cell function; cell structure; cochlea; controlled study; electrophysiology; hair cell; innervation; mouse; neurophysiology; nonhuman; null allele; phenotype; priority journal; synapse; animal; cytology; electrostimulation; genetics; hair cell; mouse mutant; olivary nucleus; physiology; Mus; Animals; Cochlea; Electric Stimulation; Electrophysiology; Hair Cells, Auditory; Mice; Mice, Knockout; Olivary Nucleus; Receptors, Nicotinic; Synapses |
Año: | 2007
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Volumen: | 104
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Número: | 51
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Página de inicio: | 20594
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Página de fin: | 20599
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DOI: |
http://dx.doi.org/10.1073/pnas.0708545105 |
Título revista: | Proceedings of the National Academy of Sciences of the United States of America
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Título revista abreviado: | Proc. Natl. Acad. Sci. U. S. A.
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ISSN: | 00278424
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CODEN: | PNASA
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CAS: | Chrna10 protein, mouse; Chrna9 protein, mouse; Receptors, Nicotinic
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PDF: | https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00278424_v104_n51_p20594_Vetter.pdf |
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v104_n51_p20594_Vetter |
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Citas:
---------- APA ----------
Vetter, D.E., Katz, E., Maison, S.F., Taranda, J.N., Turcan, S., Ballestero, J., Liberman, M.C.,..., Boulter, J.
(2007)
. The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system. Proceedings of the National Academy of Sciences of the United States of America, 104(51), 20594-20599.
http://dx.doi.org/10.1073/pnas.0708545105---------- CHICAGO ----------
Vetter, D.E., Katz, E., Maison, S.F., Taranda, J.N., Turcan, S., Ballestero, J., et al.
"The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system"
. Proceedings of the National Academy of Sciences of the United States of America 104, no. 51
(2007) : 20594-20599.
http://dx.doi.org/10.1073/pnas.0708545105---------- MLA ----------
Vetter, D.E., Katz, E., Maison, S.F., Taranda, J.N., Turcan, S., Ballestero, J., et al.
"The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system"
. Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 51, 2007, pp. 20594-20599.
http://dx.doi.org/10.1073/pnas.0708545105---------- VANCOUVER ----------
Vetter, D.E., Katz, E., Maison, S.F., Taranda, J.N., Turcan, S., Ballestero, J., et al. The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system. Proc. Natl. Acad. Sci. U. S. A. 2007;104(51):20594-20599.
http://dx.doi.org/10.1073/pnas.0708545105