Disruption of Intracellular Calcium Regulation Is Integral to Aminoglycoside-Induced Hair Cell Death

Intracellular Ca2+ is a key regulator of life or death decisions in cultured neurons and sensory cells. The role of Ca2+ in these processes is less clear in vivo, as the location of these cells often impedes visualization of intracellular Ca2+ dynamics. We generated transgenic zebrafish lines that express the genetically encoded Ca2+ indicator GCaMP in mechanosensory hair cells of the lateral line. These lines allow us to monitor intracellular Ca2+ 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 Ca2+ that occurs shortly after mitochondrial membrane potential collapse. Inhibition of intracellular Ca2+ elevation through either caged chelators or pharmacological inhibitors of Ca2+ effectors mitigates toxic effects of aminoglycoside exposure. Conversely, artificial elevation of intracellular Ca2+ by caged Ca2+ release agents sensitizes hair cells to the toxic effects of aminoglycosides. These data suggest that alterations in intracellular Ca2+ homeostasis play an essential role in aminoglycoside-induced hair cell death, and indicate several potential therapeutic targets to stem ototoxicity.

• Publication year

  2013

• Venue

  Journal of Neuroscience

• Publication date

  2013-04-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.4559-12.2013PMID 23616556PMCID PMC3703319
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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