Efferent protection from acoustic injury is mediated via alpha9 nicotinic acetylcholine receptors on outer hair cells.
Exposure to intense sound can damage the mechanosensors of the inner ear and their afferent innervation. These neurosensory elements are innervated by a sound-activated feedback pathway, the olivocochlear efferent system. One major component of this system is cholinergic, and known cholinergic effects are mediated by the alpha9/alpha10 nicotinic acetylcholine receptor (nAChR) complex. Here, we show that overexpression of alpha9 nAChR in the outer hair cells of bacterial artificial chromosome transgenic mice significantly reduces acoustic injury from exposures causing either temporary or permanent damage, without changing pre-exposure cochlear sensitivity to low- or moderate-level sound. These data demonstrate that efferent protection is mediated via the alpha9 nAChR in the outer hair cells and provide direct evidence for a protective role, in vivo, of a member of the nAChR family.
Maison
Stephane F
SF
Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114-3096, USA.
Luebke
Anne E
AE
Liberman
M Charles
MC
Zuo
Jian
J
D000595:Amino Acid Sequence; D000818:Animals; D001306:Auditory Pathways; D003051:Cochlea / Q000502:physiology; D016057:Evoked Potentials, Auditory, Brain Stem; D018072:Hair Cells, Auditory, Outer / Q000737:chemistry*; D006317:Hearing Loss, Noise-Induced / Q000517:prevention & control*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009925:Organ of Corti / Q000033:anatomy & histology / Q000502:physiology; D051381:Rats; D011978:Receptors, Nicotinic / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment
C498540:CHRNA9 protein, human; C402445:Chrna9 protein, mouse; C498541:Chrna9 protein, rat; D011978:Receptors, Nicotinic