{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:47:53Z","timestamp":1784630873487,"version":"3.55.0"},"reference-count":40,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:p> Salicylate causes a moderate hearing loss and tinnitus in humans at high-dose levels. Salicylate-induced hearing loss has been attributed to impaired sound amplification by outer hair cells (OHCs) through its direct action on the OHC motility sensor and\/or motor. However, there is a disparity of salicylate concentrations between the clinical and animal studies, i.e., extremely high extracellular concentrations of salicylate (from 1 to 10 mM) is required to produce a significant reduction of electromotility in animal studies. Such concentrations are above the clinical\/physiological range for humans. Here, we showed that clinical\/physiological concentration range of salicylate caused concentration-dependent and reversible reductions in I<jats:sub>K,n<\/jats:sub> (KCNQ4) and subsequent depolarization of OHCs. Salicylate reduced the maximal tail current of the activation curve of I<jats:sub>K,n<\/jats:sub> without altering the voltage-sensitivity ( V<jats:sub>half<\/jats:sub>). The salicylate-induced reduction of I<jats:sub>K,n<\/jats:sub> was almost completely blocked by linopirdine (0.1 mM) and BaCl<jats:sub>2<\/jats:sub> (10 mM). Consistent with the finding in OHCs, salicylate significantly reduced KCNQ4-mediated current expressed in Chinese hamster ovarian (CHO) cells by comparable amplitude to OHCs without significantly shifting V<jats:sub>half<\/jats:sub>. Nonstationary fluctuation analysis shows that salicylate significantly reduced the estimated single-channel current amplitude and numbers. Intracellular Ca<jats:sup>2+<\/jats:sup> elevation resulting from cytoplasmic acidosis also contributes to the current reduction of I<jats:sub>K,n<\/jats:sub> (KCNQ4) of OHCs. These results indicate a different model for the salicylate-induced hearing loss through the reduction of KCNQ4 and subsequent depolarization of OHCs, which reduces the driving force for transduction current and electromotility. The major mechanism underlying the reduction of I<jats:sub>K,n<\/jats:sub> (KCNQ4) is the direct blocking action of salicylate on KCNQ4. <\/jats:p>","DOI":"10.1152\/jn.01057.2009","type":"journal-article","created":{"date-parts":[[2010,2,10]],"date-time":"2010-02-10T23:24:33Z","timestamp":1265844273000},"page":"1969-1977","source":"Crossref","is-referenced-by-count":26,"title":["Effect of Salicylate on KCNQ4 of the Guinea Pig Outer Hair Cell"],"prefix":"10.1152","volume":"103","author":[{"given":"T.","family":"Wu","sequence":"first","affiliation":[{"name":"Oregon Hearing Research Center, NRC04, Department of Otolaryngology\/Head and Neck Surgery, Oregon Health Sciences University, Portland, Oregon;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Lv","sequence":"additional","affiliation":[{"name":"Program in Communication and Sensory Science, Department of Anesthesiology and Pain Medicine, Center for Neuroscience, University of California, Davis, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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