Title |
Potassium Channel Activator Attenuates Salicylate-Induced Cochlear Hearing Loss Potentially Ameliorating Tinnitus
|
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Published in |
Frontiers in Neurology, April 2015
|
DOI | 10.3389/fneur.2015.00077 |
Pubmed ID | |
Authors |
Wei Sun, Jun Liu, Chao Zhang, Na Zhou, Senthilvelan Manohar, Wendy Winchester, Jason A. Miranda, Richard J. Salvi |
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. |
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