AUTHOR=Sun Wei , Liu Jun , Zhang Chao , Zhou Na , Manohar Senthilvelan , Winchester Wendy , Miranda Jason A. , Salvi Richard J. TITLE=Potassium Channel Activator Attenuates Salicylate-Induced Cochlear Hearing Loss Potentially Ameliorating Tinnitus JOURNAL=Frontiers in Neurology VOLUME=6 YEAR=2015 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2015.00077 DOI=10.3389/fneur.2015.00077 ISSN=1664-2295 ABSTRACT=

High dose sodium salicylate causes moderate, reversible hearing loss and tinnitus. Salicylate-induced hearing loss is believed to arise from a reduction in the electromotile response of outer hair cells (OHCs) and/or reduction of KCNQ4 potassium currents in OHCs, which decreases the driving force for the transduction current. Therefore, enhancing OHC potassium currents could potentially prevent salicylate-induced temporary hearing loss. In this study, we tested whether opening voltage-gated potassium channels using ICA-105665, a novel small molecule that opens KCNQ2/3 and KCNQ3/5 channels, can reduce salicylate-induced hearing loss. We found that systemic application of ICA-105665 at 10 mg/kg prevented the salicylate-induced amplitude reduction and threshold shift in the compound action potentials recorded at the round window of the cochlea. ICA-105665 also prevented the salicylate-induced reduction of distortion-product otoacoustic emission. These results suggest that ICA-105665 partially compensates for salicylate-induced cochlear hearing loss by enhancing KCNQ2/3 and KCNQ3/5 potassium currents and the motility of OHCs.