Inositol 1,4,5-Triphosphate Receptor-Sensitive Ca2+Release, Store-Operated Ca2+ Entry, and cAMP Responsive Element Binding Protein Phosphorylation in Developing Cortical Cells following Exposure to Polychlorinated Biphenyls

摘要: The present study assessed intracellular Ca2+signaling pathways sensitive to polychlorinated biphenyls (PCBs), xenobiotics that perturb neural development and plasticity. Mobilization of Ca2+ stores after acute exposure a PCB mixture, Aroclor 1254 (A1254), as well selected congeners, was studied in P0 rat cortical neuronal culture using fluorescence microscopy. responses A1254 progressed from transient increase (lasting 3–5 min) at 1 2 μM (0.3–0.6 ppm) with store-operated influx later disturbances basal concentration; this latter pattern occurred more often 10 20 (3–6 A1254. Thapsigargin, xestospongin C, carbachol/Ca2+-free buffer blocked significantly the PCB-induced transient, whereas both ryanodine (to deplete ryanodine-sensitive stores) L-type Ca2+channel blocker nifedipine were without effect on initial transient. Both thapsigargin also latent elevations (at 0.5 h) Ca2+, depend upon extracellular entry via ion channels. Two possible consequences explored. Phosphorylation cAMP responsive element binding protein, Ca2+-activated nuclear transcription factor (CREB), an concentration-dependent manner persisted least h. Cell viability following 24-h (2–20 μM) decreased μM, but only cells cultured >6 days. This cell death did not occur apoptotic mechanism. These results indicate are associated 1) discrete alterations IP3receptor-mediated signals 2) activation downstream events impact developing cells.