In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 51 ( 2007-12-18), p. 20594-20599
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 olivo cochlear innervation and function in α 10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8–9 inner hair cells revealed ACh-gated currents in α 10 +/+ and α 10 +/− mice, with no detectable responses to ACh in α 10 −/− mice. In contrast, a proportion of α 10 −/− outer hair cells showed small ACh-evoked currents. In α 10 −/− 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, α 10 −/− 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 α 9 −/− and α 10 −/− 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 α 10 −/− mutant mice.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0708545105
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2007
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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