Disruption of intracellular calcium regulation is integral to aminoglycoside-induced hair cell death.
J Neurosci
; 33(17): 7513-25, 2013 Apr 24.
Article
en En
| MEDLINE
| ID: mdl-23616556
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Calcio
/
Células Ciliadas Vestibulares
/
Aminoglicósidos
/
Líquido Intracelular
/
Mecanorreceptores
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Neurosci
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos