ArticleFrontiers in cellular neuroscience2015
Local mechanisms for loud sound-enhanced aminoglycoside entry into outer hair cells.
Article in Frontiers in cellular neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Modulation of BK-like potassium currents by ketamine in rat cochlear outer hair cells.Molecular brain · 2026Article
- Advances in the Study of Etiology and Molecular Mechanisms of Sensorineural Hearing Loss.Cell biochemistry and biophysics · 2024Review
- Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Identifying targets to prevent aminoglycoside ototoxicity.Molecular and cellular neurosciences · 2022Review
- Mechanisms of Aminoglycoside- and Cisplatin-Induced Ototoxicity.American journal of audiology · 2021Review
- Intratympanic Lipopolysaccharide Elevates Systemic Fluorescent Gentamicin Uptake in the Cochlea.The Laryngoscope · 2021Article
- Hair Cell Protection from Ototoxic Drugs.Neural plasticity · 2021Review
- Aminoglycoside- and Cisplatin-Induced Ototoxicity: Mechanisms and Otoprotective Strategies.Cold Spring Harbor perspectives in medicine · 2019Review
- Inflammation up-regulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss.Science advances · 2019Article
- Ultrastructural localization of the likely mechanoelectrical transduction channel protein, transmembrane-like channel 1 (TMC1) during development of cochlear hair cells.Scientific reports · 2019Article
- Monitoring neonates for ototoxicity.International journal of audiology · 2018Review
- Applying U.S. national guidelines for ototoxicity monitoring in adult patients: perspectives on patient populations, service gaps, barriers and solutions.International journal of audiology · 2018Review
- Deficiency of Duffy Antigen Receptor for Chemokines Ameliorated Cochlear Damage From Noise Exposure.Frontiers in molecular neuroscience · 2018Article
- A Model for Link Pruning to Establish Correctly Polarized and Oriented Tip Links in Hair Bundles.Biophysical journal · 2017Article
- Effect of gentamicin and levels of ambient sound on hearing screening outcomes in the neonatal intensive care unit: A pilot study.International journal of pediatric otorhinolaryngology · 2017Article
- Aminoglycoside-Induced Cochleotoxicity: A Review.Frontiers in cellular neuroscience · 2017Review
- Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced Cochleotoxicity.Frontiers in cellular neuroscience · 2017Review
- Pathophysiology of the cochlear intrastrial fluid-blood barrier (review).Hearing research · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Loud sound exposure exacerbates aminoglycoside ototoxicity, increasing the risk of permanent hearing loss and degrading the quality of life in affected individuals. We previously reported that loud sound exposure induces temporary threshold shifts (TTS) and enhances uptake of aminoglycosides, like gentamicin, by cochlear outer hair cells (OHCs). Here, we explore mechanisms by which loud sound exposure and TTS could increase aminoglycoside uptake by OHCs that may underlie this form of ototoxic synergy. Mice were exposed to loud sound levels to induce TTS, and received fluorescently-tagged gentamicin (GTTR) for 30 min prior to fixation. The degree of TTS was assessed by comparing auditory brainstem responses (ABRs) before and after loud sound exposure. The number of tip links, which gate the GTTR-permeant mechanoelectrical transducer (MET) channels, was determined in OHC bundles, with or without exposure to loud sound, using scanning electron microscopy. We found wide-band noise (WBN) levels that induce TTS also enhance OHC uptake of GTTR compared to OHCs in control cochleae. In cochlear regions with TTS, the increase in OHC uptake of GTTR was significantly greater than in adjacent pillar cells. In control mice, we identified stereociliary tip links at ~50% of potential positions in OHC bundles. However, the number of OHC tip links was significantly reduced in mice that received WBN at levels capable of inducing TTS. These data suggest that GTTR uptake by OHCs during TTS occurs by increased permeation of surviving, mechanically-gated MET channels, and/or non-MET aminoglycoside-permeant channels activated following loud sound exposure. Loss of tip links would hyperpolarize hair cells and potentially increase drug uptake via aminoglycoside-permeant channels expressed by hair cells. The effect of TTS on aminoglycoside-permeant channel kinetics will shed new light on the mechanisms of loud sound-enhanced aminoglycoside uptake, and consequently on ototoxic synergy.
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