PUBLICATION
ER-Mitochondrial Calcium Flow Underlies Vulnerability of Mechanosensory Hair Cells to Damage
- Authors
- Esterberg, R., Hailey, D.W., Rubel, E.W., Raible, D.W.
- ID
- ZDB-PUB-140718-2
- Date
- 2014
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 34: 9703-19 (Journal)
- Registered Authors
- Raible, David
- Keywords
- lateral line, zebrafish
- MeSH Terms
-
- Aminoglycosides/pharmacology
- Animals
- Animals, Genetically Modified
- Calcium/metabolism*
- Cell Death/drug effects
- Chelating Agents/pharmacology
- Cytoplasm/drug effects
- Cytoplasm/metabolism
- Dose-Response Relationship, Drug
- Egtazic Acid/pharmacology
- Embryo, Nonmammalian
- Endoplasmic Reticulum/drug effects
- Endoplasmic Reticulum/genetics
- Endoplasmic Reticulum/metabolism*
- Larva
- Lateral Line System/anatomy & histology
- Mechanoreceptors/drug effects
- Mechanoreceptors/metabolism*
- Membrane Potential, Mitochondrial/drug effects
- Mitochondria/drug effects
- Mitochondria/metabolism*
- Myosin Heavy Chains/genetics
- Time Factors
- Transcription Factor Brn-3C/genetics
- Zebrafish
- PubMed
- 25031409 Full text @ J. Neurosci.
Citation
Esterberg, R., Hailey, D.W., Rubel, E.W., Raible, D.W. (2014) ER-Mitochondrial Calcium Flow Underlies Vulnerability of Mechanosensory Hair Cells to Damage. The Journal of neuroscience : the official journal of the Society for Neuroscience. 34:9703-19.
Abstract
Mechanosensory hair cells are vulnerable to environmental insult, resulting in hearing and balance disorders. We demonstrate that directional compartmental flow of intracellular Ca(2+) underlies death in zebrafish lateral line hair cells after exposure to aminoglycoside antibiotics, a well characterized hair cell toxin. Ca(2+) is mobilized from the ER and transferred to mitochondria via IP3 channels with little cytoplasmic leakage. Pharmacological agents that shunt ER-derived Ca(2+) directly to cytoplasm mitigate toxicity, indicating that high cytoplasmic Ca(2+) levels alone are not cytotoxic. Inhibition of the mitochondrial transition pore sensitizes hair cells to the toxic effects of aminoglycosides, contrasting with current models of excitotoxicity. Hair cells display efficient ER-mitochondrial Ca(2+) flow, suggesting that tight coupling of these organelles drives mitochondrial activity under physiological conditions at the cost of increased susceptibility to toxins.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping