Open AccessEffects of SERCA and PMCA inhibitors on the survival of rat cochlear hair cells during ischemia in vitro
Author(s) -
Nyamaa Amarjargal,
Birgit Mazurek,
H. Haupt,
Н. И. Андреева,
Julia Fuchs,
Johann Gross
Publication year - 2008
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931259
Subject(s) - thapsigargin , cyclopiazonic acid , serca , endocochlear potential , vanadate , cochlea , chemistry , calcium , plasma membrane ca2+ atpase , ischemia , calcium in biology , hair cell , endoplasmic reticulum , medicine , endocrinology , atpase , microbiology and biotechnology , biology , biochemistry , anatomy , enzyme
An important mechanism underlying cochlear hair cell (HC)susceptibility to hypoxia/ischemia is the influx of Ca2+. Two mainATP-dependent mechanisms contribute to maintaining low Ca2+levels: uptake of Ca2+ into intracellular stores via smoothendoplasmic reticulum calcium ATPase (SERCA) and extrusion ofCa2+ via plasma membrane calcium ATPase (PMCA). The effectsof the SERCA inhibitors thapsigargin (10 nM-10 µM) andcyclopiazonic acid (CPA; 10-50 µM) and of the PMCA blockerseosin (1.5-10 µM) and o-vanadate (1-5 mM) on inner and outerhair cells (IHCs/OHCs) were examined in normoxia and ischemiausing an in vitro model of the newborn rat cochlea. Exposure ofthe cultures to ischemia resulted in a significant loss of HCs.Thapsigargin and CPA had no effect. Eosin decreased thenumbers of IHCs and OHCs by up to 25 % in normoxia andsignificantly aggravated the ischemia-induced damage to IHCs at5 and 10 µM and to OHCs at 10 µM. o-Vanadate had no effect onIHC and OHC counts in normoxia, but aggravated the ischemiainduced HC loss in a dose-dependent manner. The effects ofeosin and o-vanadate indicate that PMCA has an important roleto play in protecting the HCs from ischemic cell death.