Response of mechanosensory hair cells of the zebrafish lateral line to aminoglycosides reveals distinct cell death pathways

Kelly N Owens; Allison B Coffin; Lisa S Hong; Keri O’Connell Bennett; Edwin W Rubel; David W Raible

doi:10.1016/j.heares.2009.03.001

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Response of mechanosensory hair cells of the zebrafish lateral line to aminoglycosides reveals distinct cell death pathways

Journal article

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Response of mechanosensory hair cells of the zebrafish lateral line to aminoglycosides reveals distinct cell death pathways

Kelly N Owens, Allison B Coffin, Lisa S Hong, Keri O’Connell Bennett, Edwin W Rubel and David W Raible

Hearing research, Vol.253(1), pp.32-41

2009

DOI: https://doi.org/10.1016/j.heares.2009.03.001

Handle:

https://hdl.handle.net/2376/106567

PMCID: PMC3167481

PMID: 19285126

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Abstract

Mechanosensory

Zebrafish

Hair cell

Lateral line

Aminoglycoside

Ototoxicity

We report a series of experiments investigating the kinetics of hair cell loss in lateral line neuromasts of zebrafish larvae following exposure to aminoglycoside antibiotics. Comparisons of the rate of hair cell loss and the differential effects of acute versus chronic exposure to gentamicin and neomycin revealed markedly different results. Neomycin induced rapid and dramatic concentration-dependent hair cell loss that is essentially complete within 90 min, regardless of concentration or exposure time. Gentamicin-induced loss of half of the hair cells within 90 min and substantial additional loss, which was prolonged and cumulative over exposure times up to at least 24 h. Small molecules and genetic mutations that inhibit neomycin-induced hair cell loss were ineffective against prolonged gentamicin exposure supporting the hypothesis that these two drugs are revealing at least two cellular pathways. The mechanosensory channel blocker amiloride blocked both neomycin and gentamicin-induced hair cell death acutely and chronically indicating that these aminoglycosides share a common entry route. Further tests with additional aminoglycosides revealed a spectrum of differential responses to acute and chronic exposure. The distinctions between the times of action of these aminoglycosides indicate that these drugs induce multiple cell death pathways.

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Title: Response of mechanosensory hair cells of the zebrafish lateral line to aminoglycosides reveals distinct cell death pathways
Creators: Kelly N Owens - Department of Biological Structure, University of Washington, Box 357420, Seattle, WA 98195-7420, USA
Allison B Coffin - Department of Otolaryngology-HNS, University of Washington, Box 356515, Seattle, WA 98195-6515, USA
Lisa S Hong - V.M. Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA 98195-7923, USA
Keri O’Connell Bennett - V.M. Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA 98195-7923, USA
Edwin W Rubel - Department of Otolaryngology-HNS, University of Washington, Box 356515, Seattle, WA 98195-6515, USA
David W Raible - Department of Biological Structure, University of Washington, Box 357420, Seattle, WA 98195-7420, USA
Publication Details: Hearing research, Vol.253(1), pp.32-41
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: Elsevier B.V
Identifiers: 99900546841701842
Language: English
Resource Type: Journal article