The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system
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 subun...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2007 |
| País: | Argentina |
| Institución: | Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales |
| Repositorio: | Biblioteca Digital (UBA-FCEN) |
| Idioma: | inglés |
| OAI Identifier: | paperaa:paper_00278424_v104_n51_p20594_Vetter |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00278424_v104_n51_p20594_Vetter |
| Access Level: | acceso abierto |
| Palabra clave: | Cochlea Electrophysiology Inner hair cells Outer hair cells nicotinic receptor nicotinic receptor alpha10 receptor subunit unclassified drug Chrna10 protein, mouse Chrna9 protein, mouse 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 mouse mutant olivary nucleus physiology Mus Animals Electric Stimulation Hair Cells, Auditory Mice Mice, Knockout Olivary Nucleus Receptors, Nicotinic Synapses |
| Sumario: | 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. |
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