@article {Esterberg7513, author = {Robert Esterberg and Dale W. Hailey and Allison B. Coffin and David W. Raible and Edwin W. Rubel}, title = {Disruption of Intracellular Calcium Regulation Is Integral to Aminoglycoside-Induced Hair Cell Death}, volume = {33}, number = {17}, pages = {7513--7525}, year = {2013}, doi = {10.1523/JNEUROSCI.4559-12.2013}, publisher = {Society for Neuroscience}, abstract = {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.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/33/17/7513}, eprint = {https://www.jneurosci.org/content/33/17/7513.full.pdf}, journal = {Journal of Neuroscience} }