Unmyelinated type II afferent neurons report cochlear damage
Unmyelinated type II afferent neurons report cochlear damage
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DOI：
10.1073/pnas.1515228112
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发表时间：
2015-11-24
影响因子：
11.1
通讯作者：
Fuchs, Paul Albert
中科院分区：
文献类型：
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作者：
Liu, Chang;Glowatzki, Elisabeth;Fuchs, Paul Albert
在哺乳动物的耳蜗中，声音信息通过主要的（95%）大直径、有髓鞘的I型传入神经传递到大脑，每个传入神经都与单个内毛细胞突触后连接。剩余的细的、无髓鞘的II型传入纤维沿着耳蜗管沿着延伸数百微米，以接触许多外毛细胞。尽管有这种广泛的乔木，II型传入神经被外毛细胞递质释放微弱激活，对声音不敏感。有趣的是，II型传入神经在耳蜗受损区域保持完整。在这里，我们表明，当外毛细胞受损时，II型传入神经被激活。这种反应依赖于亲离子型（P2X）和亲代谢型（P2Y）嘌呤能受体，结合从附近的支持细胞释放的ATP，以响应毛细胞损伤。P2Y受体的选择性激活通过关闭KCNQ型钾通道增加II型传入兴奋性，这是伴随听力损失的疼痛性超敏反应（我们称之为“noxacusis”，以区别于无疼痛的听觉过敏）的潜在机制。暴露于KCNQ通道激活剂瑞替加滨抑制了II型纤维对毛细胞损伤的反应。II型传入神经可能是耳蜗的伤害感受器，促使避免对无法修复的内耳造成进一步损害。
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.