Abstract: Background Excessive iron accumulation in the brain with oxidative damage has been found in neurodegenerative disorders and hemorrhagic stroke. The treatment of the above disorders with neural stem cells（NSCs）is a promising intervention strategy. To investigate the effects of iron overload on NSCs and explore its protection strategies is an urgent problem to be solved. Calcium channel acts as an alternative channel for iron overload in the neural cell,and hypothetically its blocker can be used to alleviate the toxic effect of iron overload on NSCs.Objective To investigate the effects of iron-overload on cell viability,apoptosis and extracellular signal-regulated kinases（ERK）phosphorylation of mouse neural stem cell line C17.2cells,and to explore the protective potential of calcium channel blockers on iron-injured C17.2cells. Methods Mouse neural stem cell line C17.2cells were used as cell models. Cell activity was detected by XTT colorimetric assay. The apoptotic cells were measured by Annexin V/propidium iodide（PI）,activated caspase-3and mitochondrial membrane potential（JC-1）,respectively,and the phosphorylation level of ERK detected by anti-phospho-ERK1/2antibody with flow cytometry. Results Iron overload significantly decreased C17.2cell viability in a dose（0.15-1.80mmol/L）and time（24-48h）-dependent manner.Furthermore,Iron overload significantly induced cell apoptosis,activated caspase-3,and caused mitochondrial damage of C17.2 cells. Calcium channel blockers（flunarizine and nimodipine）significantly alleviated apoptosis,decreased caspase-3activation,ameliorated mitochondrial damage,and increased C17.2 cells viability induced by 0.60mmol/L iron trichloride. Additionally,iron overload（0.60mmol/L）induced ERK phosphorylation of C17.2cells,which could be obviously inhibited by calcium channel blockers（flunarizine and nimodipine）.Conclusion ERK phosphorylation of mouse neural stem cell line C17.2can be induced by iron overload,which leads to mitochondria-mediated apoptosis. Calcium channel blockers can improve the iron-induced apoptosis of C17.2cells by inhibiting this process.