title: Potassium channel activator attenuates salicylate-induced cochlear hearing loss potentially ameliorating tinnitus.
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.
authors.affiliation: Center for Hearing and Deafness, State University of New York at Buffalo , Buffalo, NY , USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology, General Hospital of PLA , Beijing , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, General Hospital of PLA , Beijing , China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, Peking University Third Hospital , Beijing , China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Center for Hearing and Deafness, State University of New York at Buffalo , Buffalo, NY , USA.
authors.forename: Senthilvelan
authors.initials: S
authors.lastname: Manohar
authors.affiliation: Neusentis Research Unit, Pfizer , Cambridge , UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Winchester
authors.affiliation: Neusentis Research Unit, Pfizer , Cambridge , UK.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Miranda
authors.affiliation: Center for Hearing and Deafness, State University of New York at Buffalo , Buffalo, NY , USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Salvi
keywords: KCNQ; compound action potential; hearing loss; otoacoustic emission; salicylate