Zhao Hong-Bo, Zhu Yan, Liu Li-Man
Dept. of Otolaryngology, University of Kentucky Medical School, 800 Rose Street, Lexington, KY, 40536, USA.
Commun Biol. 2021 Jan 4;4(1):24. doi: 10.1038/s42003-020-01532-w.
Inner hair cell (IHC) ribbon synapses are the first synapse in the auditory system and can be degenerated by noise and aging, thereby leading to hidden hearing loss (HHL) and other hearing disorders. However, the mechanism underlying this cochlear synaptopathy remains unclear. Here, we report that elevation of extracellular K, which is a consequence of noise exposure, could cause IHC ribbon synapse degeneration and swelling. Like intensity dependence in noise-induced cochlear synaptopathy, the K-induced degeneration was dose-dependent, and could be attenuated by BK channel blockers. However, application of glutamate receptor (GluR) agonists caused ribbon swelling but not degeneration. In addition, consistent with synaptopathy in HHL, both K and noise exposure only caused IHC but not outer hair cell ribbon synapse degeneration. These data reveal that K excitotoxicity can degenerate IHC ribbon synapses in HHL, and suggest that BK channel may be a potential target for prevention and treatment of HHL.
内毛细胞（IHC）带状突触是听觉系统中的首个突触，会因噪声和衰老而退化，从而导致隐匿性听力损失（HHL）和其他听力障碍。然而，这种耳蜗突触病变的潜在机制仍不清楚。在此，我们报告，噪声暴露导致的细胞外钾离子升高可引起内毛细胞带状突触退化和肿胀。与噪声诱导的耳蜗突触病变中的强度依赖性一样，钾离子诱导的退化具有剂量依赖性，并且可被BK通道阻滞剂减弱。然而，应用谷氨酸受体（GluR）激动剂会导致突触带肿胀，但不会导致退化。此外，与HHL中的突触病变一致，钾离子和噪声暴露仅导致内毛细胞而非外毛细胞带状突触退化。这些数据表明，钾离子兴奋性毒性可使HHL中的内毛细胞带状突触退化，并提示BK通道可能是预防和治疗HHL的潜在靶点。
