Extracellular divalent cations modulate aminoglycoside-induced hair cell death in the zebrafish lateral line

Allison B Coffin; Katherine E Reinhart; Kelly N Owens; David W Raible; Edwin W Rubel

doi:10.1016/j.heares.2009.03.004

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Extracellular divalent cations modulate aminoglycoside-induced hair cell death in the zebrafish lateral line

Journal article

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Extracellular divalent cations modulate aminoglycoside-induced hair cell death in the zebrafish lateral line

Allison B Coffin, Katherine E Reinhart, Kelly N Owens, David W Raible and Edwin W Rubel

Hearing research, Vol.253(1), pp.42-51

2009

DOI: https://doi.org/10.1016/j.heares.2009.03.004

Handle:

https://hdl.handle.net/2376/109544

PMCID: PMC5139914

PMID: 19285547

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https://doi.org/10.1016/j.heares.2009.03.004View

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Abstract

Hair cell

Lateral line

Magnesium

Calcium

Aminoglycoside

Ototoxicity

Aminoglycoside antibiotics cause death of sensory hair cells. Research over the past decade has identified several key players in the intracellular cascade. However, the role of the extracellular environment in aminoglycoside ototoxicity has received comparatively little attention. The present study uses the zebrafish lateral line to demonstrate that extracellular calcium and magnesium ions modulate hair cell death from neomycin and gentamicin in vivo, with high levels of either divalent cation providing significant protection. Imaging experiments with fluorescently-tagged gentamicin show that drug uptake is reduced under high calcium conditions. Treating fish with the hair cell transduction blocker amiloride also reduces aminoglycoside uptake, preventing the toxicity, and experiments with variable calcium and amiloride concentrations suggest complementary effects between the two protectants. Elevated magnesium, in contrast, does not appear to significantly attenuate drug uptake, suggesting that the two divalent cations may protect hair cells from aminoglycoside damage through different mechanisms. These results provide additional evidence for calcium- and transduction-dependent aminoglycoside uptake. Divalent cations provided differential protection from neomycin and gentamicin, with high cation concentrations almost completely protecting hair cells from neomycin and acute gentamicin toxicity, but offering reduced protection from continuous (6 h) gentamicin exposure. These experiments lend further support to the hypothesis that aminoglycoside toxicity occurs via multiple pathways in a both a drug and time course-specific manner.

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Title: Extracellular divalent cations modulate aminoglycoside-induced hair cell death in the zebrafish lateral line
Creators: Allison B Coffin - Virginia Merrill Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA 98195, USA
Katherine E Reinhart - Virginia Merrill Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA 98195, USA
Kelly N Owens - Virginia Merrill Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA 98195, USA
David W Raible - Virginia Merrill Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA 98195, USA
Edwin W Rubel - Virginia Merrill Bloedel Hearing Research Center, University of Washington, Box 357923, Seattle, WA 98195, USA
Publication Details: Hearing research, Vol.253(1), pp.42-51
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: Elsevier B.V
Identifiers: 99900547197101842
Language: English
Resource Type: Journal article