Abstract: Objective To explore the protective potential of calcium channel blockers on iron-injured primary neural stem cells. Methods Rat embryonic（E17.5）hippocampal neural stem cells（hNSC）served as a cell model. Immunostaining method was used to identify the characteristics of hNSC,while reverse transcription-polymerase chain reaction（RT-PCR）,immunostaing and flow cytometry methods was respectively adopted to confirm the expression of mRNA and protein of L type calcium channel Cav1.2gene of hNSC. XTT colorimetric method was used to detect the cell viability. The Annexin V/propidium iodide（PI）was used to measure apoptotic cells,while anti-phospho-extracellular regulated protein kinase（ERK）1/2was adopted to detect ERK phosphorylation,both via flow cytometry. The hNSC were divided into the control,iron-overload（0.9mmol/L）,calcium channel blockers（flunarizine 0.1μmol/L or nimodipine 10nmol/L）or mitogen-activated protein kinase（MAPK）/ERK kinase（MEK）inhibitor（U0126）,and calcium channel blockers or U0126 plus iron-overload groups,to explore the effects of calcium channel blockers or MEK inhibitor on cell viability as well as apoptosis of iron-injured hNSC. Results The hNSC showed typical characteristics of neural stem cells,and expressed mRNA（158bp）as well as relevant protein of Cav1.2gene of L-type calcium channel.Calcium channel blockers could alleviate clinically relevant doses of iron（0.9mmol/L）induced apoptosis,and increased cell viability of hNSC（nimodipine P＜0.01）. Clinically relevant doses of iron induce ERK activation of hNSC,and MEK inhibitor（U0126）could significantly increase cell viability of hNSC（P＜0.01）in clinically relevant dose of iron-overloaded. Conclusion Calcium channel blockers could potentially protect iron-induced neurotoxicity in hNSC,probably by inhibiting ERK activation.