Disruption of intracellular calcium regulation is integral to aminoglycoside-induced hair cell death

Robert Esterberg; Dale W Hailey; Allison B Coffin; David W Raible; Edwin W Rubel

doi:10.1523/JNEUROSCI.4559-12.2013

Back

Disruption of intracellular calcium regulation is integral to aminoglycoside-induced hair cell death

Journal article

Open access

Peer reviewed

Disruption of intracellular calcium regulation is integral to aminoglycoside-induced hair cell death

Robert Esterberg, Dale W Hailey, Allison B Coffin, David W Raible and Edwin W Rubel

The Journal of neuroscience, Vol.33(17), pp.7513-7525

04/24/2013

DOI: https://doi.org/10.1523/JNEUROSCI.4559-12.2013

Handle:

https://hdl.handle.net/2376/116580

PMCID: PMC3703319

PMID: 23616556

Files and links (1)

url

https://doi.org/10.1523/JNEUROSCI.4559-12.2013View

Published (Version of record) Open

Abstract

Animals, Genetically Modified

Mechanoreceptors - physiology

Male

Zebrafish

Cytoplasm - physiology

Intracellular Fluid - physiology

Hair Cells, Vestibular - physiology

Intracellular Fluid - drug effects

Animals

Calcium - physiology

Cell Death - physiology

Aminoglycosides - toxicity

Mechanoreceptors - drug effects

Hair Cells, Vestibular - drug effects

Lateral Line System - drug effects

Lateral Line System - physiology

Female

Cell Death - drug effects

Cytoplasm - drug effects

Intracellular Ca(2+) is a key regulator of life or death decisions in cultured neurons and sensory cells. The role of Ca(2+) in these processes is less clear in vivo, as the location of these cells often impedes visualization of intracellular Ca(2+) dynamics. We generated transgenic zebrafish lines that express the genetically encoded Ca(2+) indicator GCaMP in mechanosensory hair cells of the lateral line. These lines allow us to monitor intracellular Ca(2+) dynamics in real time during aminoglycoside-induced hair cell death. After exposure of live larvae to aminoglycosides, dying hair cells undergo a transient increase in intracellular Ca(2+) that occurs shortly after mitochondrial membrane potential collapse. Inhibition of intracellular Ca(2+) elevation through either caged chelators or pharmacological inhibitors of Ca(2+) effectors mitigates toxic effects of aminoglycoside exposure. Conversely, artificial elevation of intracellular Ca(2+) by caged Ca(2+) release agents sensitizes hair cells to the toxic effects of aminoglycosides. These data suggest that alterations in intracellular Ca(2+) homeostasis play an essential role in aminoglycoside-induced hair cell death, and indicate several potential therapeutic targets to stem ototoxicity.

Metrics

8 Record Views

See more details

Details

Title: Disruption of intracellular calcium regulation is integral to aminoglycoside-induced hair cell death
Creators: Robert Esterberg - Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195, USA
Dale W Hailey
Allison B Coffin
David W Raible
Edwin W Rubel
Publication Details: The Journal of neuroscience, Vol.33(17), pp.7513-7525
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: United States
Grant note: S10 RR026826 / NCRR NIH HHS DC99312 / NIDCD NIH HHS DC012244 / NIDCD NIH HHS DC010940 / NIDCD NIH HHS F32 DC010940 / NIDCD NIH HHS P30 DC004661 / NIDCD NIH HHS R03 DC012881 / NIDCD NIH HHS F32 DC012244 / NIDCD NIH HHS R01 DC005987 / NIDCD NIH HHS DC05987 / NIDCD NIH HHS
Identifiers: 99900548082201842
Language: English
Resource Type: Journal article