title: Endoplasmic reticulum dysfunction and Ca2+ deregulation in isolated CA1 neurons during oxygen and glucose deprivation.
abstract: Intracellular calcium ([Ca2+]i) plays a pivotal role in neuronal ischemia. The aim of the present study was to investigate the routes of Ca2+ entry during non-excitotoxic oxygen and glucose deprivation (OGD) in acutely dissociated rat CA1 neurons. During OGD the fluo-3/fura red ratio reflecting [Ca2+]i increased rapidly and irreversibly. [Ca2+]i increased to the same degree in Ca2 + depleted medium, and also when both the ryanodine receptors (RyR) and the inositol 1,4,5-trisphosphate (IP3) receptors were blocked. When the endoplasmic reticulum (ER) Ca2+ stores were emptied with thapsigargin no increase in [Ca2+]i was observed independent of extracellular Ca2+. The OGD induced Ca2+ deregulation in isolated CA1 neurons is not prevented by removing Ca2+, or by blocking the IP3- or RyR receptors. However, when SERCA was blocked, no increase in [Ca2+]i was observed suggesting that SERCA dysfunction represents an important mechanism for ischemic Ca2+ overload.
authors.affiliation: Institute for Surgical Research, Department of Neurosurgery, National Hospital, Rikshospitalet, N-0027, Oslo, Norway. g.a.larsen@labmed.uio.no
authors.forename: Geir Arne
authors.initials: GA
authors.lastname: Larsen
authors.forename: Havard K
authors.initials: HK
authors.lastname: Skjellegrind
authors.forename: Morten C
authors.initials: MC
authors.lastname: Moe
authors.forename: Morten Larsen
authors.initials: ML
authors.lastname: Vinje
authors.forename: Jon
authors.initials: J
authors.lastname: Berg-Johnsen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003470:Culture Media; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D003470:Culture Media; D019284:Thapsigargin; D005947:Glucose; D010100:Oxygen; D002118:Calcium