Prevention and treatment of noise-induced hearing loss and cochlear synapse degeneration by potassium channel blockers in vivo.

UNLABELLED: Noise can induce hearing loss. In particularly, noise can induce cochlear synapse degeneration leading to hidden hearing loss, which is the most common type of hearing disorders in the clinic. Currently, there is no pharmacological treatment, particularly, no post-exposure (i.e., therapeutic) treatment available in the clinic. Here, we report that systematic administration of K + channel blockers before or after noise exposure could significantly attenuate NIHL and synapse degeneration. After systematic administration of a general K-channel blocker tetraethylammonium (TEA), the elevation of auditory brainstem response (ABR) thresholds after noise-exposure significantly reduced, and the active cochlear mechanics significantly improved. The therapeutic effect was further improved as the post-exposure administration time extending to 3 days. BK channel is a predominant K + channel in the inner hair cells. Systematic administration of a BK channel blocker GAL-021 after noise exposure also ameliorated hearing loss and improved hearing behavioral responses tested by acoustic startle response (ASR). Finally, both TEA and GAL-021 significantly attenuated noise-induced ribbon synapse degeneration. These data demonstrate that K + -channel blockers can prevent and treat NIHL and cochlear synapse degeneration. Our finding may aid in developing therapeutic strategies for post-exposure treatment of NIHL and synapse degeneration.

SIGNIFICANCE STATEMENT: Noise is a common deafness factor affecting more 100 million people in the United States. So far, there is no pharmacological treatment available. We show here that administration of K + channel blockers after noise exposure could attenuate noise-induced hearing loss and synapse degeneration, and improved behavioral responses. This is the first time to real the K + channel blockers that could treat noise-induced hearing loss and cochlear synaptopathy after noise exposure.