An important mechanism underlying cochlear hair cell (HC) susceptibility to hypoxia/ischemia is the influx of Ca2+. Two main ATP-dependent mechanisms contribute to maintaining low Ca2+ levels: uptake of Ca2+ into intracellular stores via smooth endoplasmic reticulum calcium ATPase (SERCA) and extrusion of Ca2+ via plasma membrane calcium ATPase (PMCA). The effects of the SERCA inhibitors thapsigargin (10 nM-10 µM) and cyclopiazonic acid (CPA; 10-50 µM) and of the PMCA blockers eosin (1.5-10 µM) and o-vanadate (1-5 mM) on inner and outer hair cells (IHCs/OHCs) were examined in normoxia and ischemia using an in vitro model of the newborn rat cochlea. Exposure of the cultures to ischemia resulted in a significant loss of HCs. Thapsigargin and CPA had no effect. Eosin decreased the numbers of IHCs and OHCs by up to 25 % in normoxia and significantly aggravated the ischemia-induced damage to IHCs at 5 and 10 µM and to OHCs at 10 µM. o-Vanadate had no effect on IHC and OHC counts in normoxia, but aggravated the ischemiainduced HC loss in a dose-dependent manner. The effects of eosin and o-vanadate indicate that PMCA has an important role to play in protecting the HCs from ischemic cell death.
- Klíčová slova
- Calcium, Organ of Corti, Ischemia, PMCA, Rat,
- MeSH
- ATPasy přenášející vápník přes plazmatickou membránu antagonisté a inhibitory MeSH
- Cortiho orgán cytologie fyziologie MeSH
- eosin farmakologie MeSH
- financování organizované MeSH
- inhibitory enzymů farmakologie MeSH
- ischemie enzymologie MeSH
- krysa rodu rattus MeSH
- novorozená zvířata MeSH
- perilymfa fyziologie MeSH
- potkani Wistar MeSH
- sarkoplazmatická Ca2+-ATPáza antagonisté a inhibitory MeSH
- vanadáty farmakologie MeSH
- vápník metabolismus MeSH
- viabilita buněk fyziologie MeSH
- vnější vláskové buňky účinky léků MeSH
- vnitřní vláskové buňky účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
