The alpha10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system

VETTER D; KATZ E; MAISON, S.F; TARANDA J; SEVIN T; BALLESTERO J; LIBERMAN, M.C.; ELGOYHEN AB; BOULTER J

Proceedings of the National Academy of Science, USA

Año: 2007 vol. 104 p. 20594 - 20599

Although homomeric channels assembled from the a9 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 a9 and a10 subunits. To gain insight into a10 subunit function in vivo, we examined olivocochlear innervation and function in a10 null mutant mice. Electrophysiological recordings from P8-9 inner hair cells revealed ACh-gated currents in a10+/+ and a10+/- mice, with no detectable responses to ACh in a10-/- mice. In contrast, a proportion of a10-/- outer hair cells showed small ACh-evoked currents. In a10-/- mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual a9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, a10-/- 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 a9-/- and a10-/- mice have overlapping but non-identical phenotypes. Moreover, a10 nAChR subunits are required for normal olivocochlear activity since a9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in a10-/- mutant mice.