ArticleJournal of the Association for Research in Otolaryngology : JARO2011
TRPA1-mediated accumulation of aminoglycosides in mouse cochlear outer hair cells.
Article in Journal of the Association for Research in Otolaryngology : JARO, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 82 citations in OpenAlex.
- The Blood-Labyrinth Barrier: Non-Invasive Delivery Strategies for Inner Ear Drug Delivery.Pharmaceutics · 2025Review
- Inhibition of GABARAP or GABARAPL1 prevents aminoglycoside- induced hearing loss.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Protective effects of MET channels on aminoglycosides- and cisplatin-induced ototoxicity.International journal of medical sciences · 2025Review
- TRP channels in mammalian hearing loss.Frontiers in molecular neuroscience · 2025Review
- Transient Receptor Potential (TRP) Channels in Cochlear Function: Looking Beyond Mechanotransduction.Journal of the Association for Research in Otolaryngology : JARO · 2024Article
- Otoprotection against aminoglycoside- and cisplatin-induced ototoxicity focusing on the upstream drug uptake pathway.Journal of the Chinese Medical Association : JCMA · 2024Review
- Mechanisms and Impact of Aminoglycoside-Induced Vestibular Deficits.American journal of audiology · 2023Review
- TRPA1 activation in non-sensory supporting cells contributes to regulation of cochlear sensitivity after acoustic trauma.Nature communications · 2023Article
- Mechanisms and otoprotective strategies of programmed cell death on aminoglycoside-induced ototoxicity.Frontiers in cell and developmental biology · 2023Review
- Identifying targets to prevent aminoglycoside ototoxicity.Molecular and cellular neurosciences · 2022Review
- In vivo real-time imaging reveals megalin as the aminoglycoside gentamicin transporter into cochlea whose inhibition is otoprotective.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Pitavastatin protects against neomycin-induced ototoxicity through inhibition of endoplasmic reticulum stress.Frontiers in molecular neuroscience · 2022Article
- Mechanisms of Ototoxicity and Otoprotection.Otolaryngologic clinics of North America · 2021Review
- Pharmacokinetic modelling to predict risk of ototoxicity with intravenous tobramycin treatment in cystic fibrosis.The Journal of antimicrobial chemotherapy · 2021Article
- Mechanisms of Aminoglycoside- and Cisplatin-Induced Ototoxicity.American journal of audiology · 2021Review
- Hair Cell Protection from Ototoxic Drugs.Neural plasticity · 2021Review
- Cannabinoid Signaling in Auditory Function and Development.Frontiers in molecular neuroscience · 2021Article
- Systemic Fluorescent Gentamicin Enters Neonatal Mouse Hair Cells Predominantly Through Sensory Mechanoelectrical Transduction Channels.Journal of the Association for Research in Otolaryngology : JARO · 2020Article
- Berbamine Analogs Exhibit Differential Protective Effects From Aminoglycoside-Induced Hair Cell Death.Frontiers in cellular neuroscience · 2020Article
- Aminoglycoside- and Cisplatin-Induced Ototoxicity: Mechanisms and Otoprotective Strategies.Cold Spring Harbor perspectives in medicine · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Aminoglycoside ototoxicity involves the accumulation of antibiotic molecules in the inner ear hair cells and the subsequent degeneration of these cells. The exact route of entry of aminoglycosides into the hair cells in vivo is still unknown. Similar to other small organic cations, aminoglycosides could be brought into the cell by endocytosis or permeate through large non-selective cation channels, such as mechanotransduction channels or ATP-gated P2X channels. Here, we show that the aminoglycoside antibiotic gentamicin can enter mouse outer hair cells (OHCs) via TRPA1, non-selective cation channels activated by certain pungent compounds and by endogenous products of lipid peroxidation. Using conventional and perforated whole-cell patch clamp recordings, we found that application of TRPA1 agonists initiates inward current responses in wild-type OHCs, but not in OHCs of homozygous Trpa1 knockout mice. Similar responses consistent with the activation of non-selective cation channels were observed in heterologous cells transfected with mouse Trpa1. Upon brief activation with TRPA1 agonists, Trpa1-transfected cells become loaded with fluorescent gentamicin-Texas Red conjugate (GTTR). This uptake was not observed in mock-transfected or non-transfected cells. In mouse organ of Corti explants, TRPA1 activation resulted in the rapid entry of GTTR and another small cationic dye, FM1-43, in OHCs and some supporting cells, even when hair cell mechanotransduction was disrupted by pre-incubation in calcium-free solution. This TRPA1-mediated entry of GTTR and FM1-43 into OHCs was observed in wild-type but not in Trpa1 knockout mice and was not blocked by PPADS, a non-selective blocker of P2X channels. Notably, TRPA1 channels in mouse OHCs were activated by 4-hydroxynonenal, an endogenous molecule that is known to be generated during episodes of oxidative stress and accumulate in the cochlea after noise exposure. We concluded that TRPA1 channels may provide a novel pathway for the entry of aminoglycosides into OHCs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.