Excess extracellular K⁺ causes inner hair cell ribbon synapse degeneration

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.