title: Traumatic injury of cortical neurons causes changes in intracellular calcium stores and capacitative calcium influx.
abstract: Using an in vitro traumatic injury model, we examined the effects of mechanical (stretch) injury on intracellular Ca2+ store-mediated signaling in cultured cortical neurons using fura-2. We previously found that elevation of [Ca2+](i) by the endoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, was abolished 15 min post-injury. In the current studies, pre-injury inhibition of phospholipase C with neomycin sulfate maintained Ca2+-replete stores 15 min post-injury, suggesting that the initial injury-induced store depletion may be due to increased inositol trisphosphate production. Thapsigargin-stimulated elevation of [Ca2+](i) returned with time after injury and was potentiated at 3 h. Stimulation with thapsigargin in Ca2+-free media revealed that the size of the Ca2+ stores was normal at 3 h post-injury. However, Ca2+ influx triggered by depletion of intracellular Ca2+ stores (capacitative Ca2+ influx) was enhanced 3 h after injury. Enhancement was blocked by inhibitors of cytosolic phospholipase A2 and cytochrome P450 epoxygenase. Since intracellular Ca2+ store-mediated signaling plays an important role in neuronal function, the observed changes may contribute to dysfunction produced by traumatic brain injury. Additionally, our results suggest that capacitative Ca2+ influx may be mediated by both conformational coupling and a diffusible messenger synthesized by the combined action of cytosolic PLA2 and P450.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0613, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Weber
authors.forename: B A
authors.initials: BA
authors.lastname: Rzigalinski
authors.forename: E F
authors.initials: EF
authors.lastname: Ellis
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D018920:Coculture Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D017136:Ion Transport; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium