The 10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system

Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2008; 104(51):20594-9. DOI: 10.1073/pnas.0708545105
Source: PubMed


Although homomeric channels assembled from the alpha9 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 alpha9 and alpha10 subunits. To gain insight into alpha10 subunit function in vivo, we examined olivo cochlear innervation and function in alpha10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in alpha10(+/+) and alpha10(+/-) mice, with no detectable responses to ACh in alpha10(-/-) mice. In contrast, a proportion of alpha10(-/-) outer hair cells showed small ACh-evoked currents. In alpha10(-/-) mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual alpha9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, alpha10(-/-) 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 alpha9(-/-) and alpha10(-/-) mice have overlapping but nonidentical phenotypes. Moreover, alpha10 nAChR subunits are required for normal olivocochlear activity because alpha9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in alpha10(-/-) mutant mice.

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    • "We tested changes in Prestin protein expression by Western blot after unilateral conductive hearing loss as a measure of regulation by acoustic input imbalance, and compared this with changes in Prestin protein expression after unilateral AC ablation. In parallel, because OHC electromotility regulation by MOC involves specialized cholinergic neurotransmission, we tested by qRT-PCR whether the expression of the alpha10 nAChR gene mRNA, a staple of cholinergic neurotransmission at the MOC-OHC synapse (Dallos et al., 1997; Maison et al., 2002, 2007; Batta et al., 2004; Vetter et al., 2007), changes along with the expression of Prestin and β-actin genes, as cell markers of the effects of MOC inactivation on OHC electromotility. "
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