title: Unmyelinated type II afferent neurons report cochlear damage.
abstract: In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term "noxacusis" to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber's response to hair cell damage. Type II afferents may be the cochlea's nociceptors, prompting avoidance of further damage to the irreparable inner ear.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Glowatzki
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205 pfuchs1@jhmi.edu.
authors.forename: Paul Albert
authors.initials: PA
authors.lastname: Fuchs
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D003051:Cochlea / Q000294:innervation* / Q000473:pathology*; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000473:pathology; D015640:Ion Channel Gating / Q000187:drug effects; D007477:Ions; D051656:KCNQ Potassium Channels / Q000378:metabolism; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000473:pathology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000473:pathology*; D011188:Potassium / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D058470:Receptors, Purinergic P2Y / Q000378:metabolism
chemical_list: D007477:Ions; D051656:KCNQ Potassium Channels; D017470:Receptors, Glutamate; D058470:Receptors, Purinergic P2Y; D000255:Adenosine Triphosphate; D011188:Potassium
keywords: ATP; acoustic trauma; hyperacusis; noxacusis; type II cochlear afferents