Inhibition of K+ currents of outer hair cells in guinea pig cochlea by fluoxetine

Bian, Jing; Yeh, Jay Z.; Aistrup, Gary L.; Narahashi, Toshio; Moore, Ernest J.

doi:10.1016/s0014-2999(02)02421-4

Cited by 9 publications

(6 citation statements)

References 28 publications

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“…Airhart et al (2007) showed that zebrafish exposed to fluoxetine exhibit movement disorders, but whether this effect is related to hair cell function in lateral line, vestibular or hearing organs or to other systemic effects is unknown. Fluoxetine can inhibit potassium currents in guinea pig hair cells, an effect not mediated by the serotonin reuptake channel, but rather by blocking the SK-type potassium channel (Bian, et al, 2002; Terstappen, et al, 2003). This suggests that an off-target effect, blockage of potassium channels, may afford hair cells protection from toxins.…”

Section: Discussionmentioning

confidence: 99%

Screen of FDA-approved drug library reveals compounds that protect hair cells from aminoglycosides and cisplatin

et al. 2012

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Loss of mechanosensory hair cells in the inner ear accounts for many hearing loss and balance disorders. Several beneficial pharmaceutical drugs cause hair cell death as a side effect. These include aminoglycoside antibiotics, such as neomycin, kanamycin and gentamicin, and several cancer chemotherapy drugs, such as cisplatin. Discovering new compounds that protect mammalian hair cells from toxic insults is experimentally difficult because of the inaccessibility of the inner ear. We used the zebrafish lateral line sensory system as an in vivo screening platform to survey a library of FDA-approved pharmaceuticals for compounds that protect hair cells from neomycin, gentamicin, kanamycin and cisplatin. Ten compounds were identified that provide protection from at least two of the four toxins. The resulting compounds fall into several drug classes, including serotonin and dopamine-modulating drugs, adrenergic receptor ligands, and estrogen receptor modulators. The protective compounds show different effects against the different toxins, supporting the idea that each toxin causes hair cell death by distinct, but partially overlapping, mechanisms. Furthermore, some compounds from the same drug classes had different protective properties, suggesting that they might not prevent hair cell death by their known target mechanisms. Some protective compounds blocked gentamicin uptake into hair cells, suggesting that they may block mechanotransduction or other routes of entry. The protective compounds identified in our screen will provide a starting point for studies in mammals as well as further research discovering the cellular signaling pathways that trigger hair cell death.

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Section: Discussionmentioning

confidence: 99%

Screen of FDA-approved drug library reveals compounds that protect hair cells from aminoglycosides and cisplatin

et al. 2012

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“…A corollary to this concept is that elevated prestin levels in a mutant OHC would increase this risk. This process could potentiate the large leak currents that are already present in OHCs (Beurg et al 2009;Bian et al 2002;Fuchs 1992;Housley and Ashmore 1992;O'Beirne and Patuzzi 2007), overwhelm a cell's ability to regulate its intracellular ion concentrations, and drive it towards necrosis or apoptosis. As well, there may be other underlying differences in the OHC membrane between Tecta genotypes that affect their susceptibility to electrical stimulation.…”

Section: Discussionmentioning

confidence: 99%

Biophysical Mechanisms Underlying Outer Hair Cell Loss Associated with a Shortened Tectorial Membrane

Liu

Gao

Tao

et al. 2011

JARO

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The tectorial membrane (TM) connects to the stereociliary bundles of outer hair cells (OHCs). Humans with an autosomal dominant C1509G mutation in alpha-tectorin, a protein constituent of the TM, are born with a partial hearing loss that worsens over time. The Tecta C1509/+ transgenic mouse with the same point mutation has partial hearing loss secondary to a shortened TM that only contacts the first row of OHCs. As well, Tecta C1509G/+ mice have increased expression of the OHC electromotility protein, prestin. We sought to determine whether these changes impact OHC survival. Distortion product otoacoustic emission thresholds in a quiet environment did not change to 6 months of age. However, noise exposure produced acute threshold shifts that fully recovered in Tecta +/+ mice but only partially recovered in Tecta C1509G/+ mice. While Tecta +/+ mice lost OHCs primarily at the base and within all three rows, Tecta C1509G/+ mice lost most of their OHCs in a more apical region of the cochlea and nearly completely within the first row. In order to estimate the impact of a shorter TM on the forces faced by the stereocilia within the first OHC row, both the wild type and the heterozygous conditions were simulated in a computational model. These analyses predicted that the shear force on the stereocilia is~50% higher in the heterozygous condition. We then measured electrically induced movements of the reticular lamina in situ and found that while they decreased to the noise floor in prestin null mice, they were increased by 4.58 dB in Tecta C1509G/+ mice compared to Tecta +/+ mice. The increased movements were associated with a fourfold increase in OHC death as measured by vital dye staining. Together, these findings indicate that uncoupling the TM from some OHCs leads to partial hearing loss and places the remaining coupled OHCs at higher risk. Both the mechanics of the malformed TM and the increased prestin-related movements of the organ of Corti contribute to this higher risk profile.

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“…In addition, it has been shown to block the effects of intense stress on behaviour and the cardiovascular system in an animal model of post‐traumatic stress disorder . Recent studies have shown that other antidepressant agents, such as fluoxetine, also affect hair follicles in animals . Hence, we decided to investigate the effects of tianeptine on UWS‐induced AA‐like lesions in mice.…”

Section: Discussionmentioning

confidence: 99%

“…Tianeptine is an antidepressant with memory‐protective properties that increases serotonin uptake in the brain. Recent studies have shown that other antidepressant agents, such as fluoxetine, affect the hair follicles in animals . In this study, we investigated whether tianeptine could inhibit the effects of catagen induction in AA‐like lesions induced by ultrasonic wave stress (UWS) in mice.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of tianeptine on catagen induction in alopecia areata-like lesions induced by ultrasonic wave stress in mice

et al. 2013

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Inhibition of K+ currents of outer hair cells in guinea pig cochlea by fluoxetine

Cited by 9 publications

References 28 publications

Screen of FDA-approved drug library reveals compounds that protect hair cells from aminoglycosides and cisplatin

Screen of FDA-approved drug library reveals compounds that protect hair cells from aminoglycosides and cisplatin

Biophysical Mechanisms Underlying Outer Hair Cell Loss Associated with a Shortened Tectorial Membrane

Inhibitory effect of tianeptine on catagen induction in alopecia areata-like lesions induced by ultrasonic wave stress in mice

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