Abstract
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.
Highlights
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
In comparison with those in the normal extracellular solution (NES) group, the presynaptic ribbon, postsynaptic glutamate receptor (GluR), and synapse per IHC in the high-K+ group were reduced to 62.5 ± 3.20, 83.4 ± 5.94, and 60.8 ± 5.58% (P = 1.4E−05, 0.02, and 0.0008, paired ttest, two-tail), respectively (Fig. 1b)
To assess the effect of glutamate excitotoxicity on the IHC ribbon synapse degeneration, we investigated the effect of GluR agonists on IHC ribbon degeneration
Summary
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. Consistent with synaptopathy in HHL, both K+ and noise exposure only caused IHC but not outer hair cell ribbon synapse degeneration. It has been found that exposure to moderate levels of noise, even short-term, can cause extensive degeneration of ribbon synapses between inner hair cells (IHCs) and auditory nerves without hair cell loss[1,2,3,4] This cochlear synaptopathy can cause hidden hearing loss (HHL), which presents with a normal audiogram with difficulty in hearing speech in noisy environments[2,5,6]. A recent study demonstrated that noise could still induce ribbon synapse swelling in mice lacking vesicular glutamate transporter-3 with deficiency in release of glutamate[18] These data suggest that other mechanisms glutamate excitotoxicity have an important role in the ribbon synapse degeneration. These data suggest that K+ excitotoxicity may play a major role in the IHC ribbon synapse degeneration, thereby shedding light on the prevention and treatment of this common type of hearing loss
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