{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:34:50Z","timestamp":1788914090140,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Deafness and other Communication Disorders (NIDCD)","award":["DC DC018786"],"award-info":[{"award-number":["DC DC018786"]}]},{"name":"National Institute on Deafness and other Communication Disorders (NIDCD)","award":["AG073997"],"award-info":[{"award-number":["AG073997"]}]},{"name":"National Institute on Aging (NIA)","award":["DC DC018786"],"award-info":[{"award-number":["DC DC018786"]}]},{"name":"National Institute on Aging (NIA)","award":["AG073997"],"award-info":[{"award-number":["AG073997"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previous studies have suggested a role for selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac\u00ae) in the treatment of dizziness and inner ear vestibular dysfunction. The potential mechanism of action within the vestibular system remains unclear; however, fluoxetine has been reported to block certain types of K+ channel in other systems. Here, we investigated the direct actions of fluoxetine on membrane currents in presynaptic hair cells and postsynaptic calyx afferents of the gerbil peripheral vestibular system using whole cell patch clamp recordings in crista slices. We explored differences in K+ currents in peripheral zone (PZ) and central zone (CZ) calyces of the crista and their response to fluoxetine application. Outward K+ currents in PZ calyces showed greater inactivation at depolarized membrane potentials compared to CZ calyces. The application of 100 \u03bcM fluoxetine notably reduced K+ currents in calyx terminals within both zones of the crista, and the remaining currents exhibited distinct traits. In PZ cells, fluoxetine inhibited a non-inactivating K+ current and revealed a rapidly activating and inactivating K+ current, which was sensitive to blocking by 4-aminopyridine. This was in contrast to CZ calyces, where low-voltage-activated and non-inactivating K+ currents persisted following application of 100 \u03bcM fluoxetine. Additionally, marked inhibition of transient inward Na+ currents by fluoxetine was observed in calyces from both crista zones. Different concentrations of fluoxetine were tested, and the EC50 values were found to be 40 \u00b5M and 32 \u00b5M for K+ and Na+ currents, respectively. In contrast, 100 \u03bcM fluoxetine had no impact on voltage-dependent K+ currents in mechanosensory type I and type II vestibular hair cells. In summary, micromolar concentrations of fluoxetine are expected to strongly reduce both Na+ and K+ conductance in afferent neurons of the peripheral vestibular system in vivo. This would lead to inhibition of action potential firing in vestibular sensory neurons and has therapeutic implications for disorders of balance.<\/jats:p>","DOI":"10.3390\/ijms25168801","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T05:23:27Z","timestamp":1723613007000},"page":"8801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of Ionic Currents by Fluoxetine in Vestibular Calyces in Different Epithelial Loci"],"prefix":"10.3390","volume":"25","author":[{"given":"Nesrien M. M.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head & Neck Surgery, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances L.","family":"Meredith","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head & Neck Surgery, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5624-4993","authenticated-orcid":false,"given":"Katherine J.","family":"Rennie","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head & Neck Surgery, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1176\/appi.psy.46.4.334","article-title":"Fluoxetine for vestibular dysfunction and anxiety: A prospective pilot study","volume":"46","author":"Simon","year":"2005","journal-title":"Psychosomatics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3233\/VES-230045","article-title":"Effect of public square dancing combined with serotonin reuptake inhibitors on persistent postural-perceptual dizziness (PPPD) in middle-aged and older women","volume":"34","author":"Tang","year":"2024","journal-title":"J. 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