| Abstract: | In the present study, we investigated the mechanisms underlying the mediation of iron transport by Ltype Ca~(2+)channels(LTCCs) in primary cultured ventral mesencephalon(VM) neurons from rats. We found that cotreatment with 100 lmol/L FeSO_4 and MPP~+ (1-methyl-4-phenylpyridinium) significantly increased the production of intracellular reactive oxygen species, decreased the mitochondrial transmembrane potential and increased the caspase-3 activation compared to MPP~+ treatment alone.Co-treatment with 500 lmol/L CaCl_2 further aggravated the FeSO_4-induced neurotoxicity in MPP~+ -treated VM neurons. Co-treatment with 10 lmol/L isradipine, an LTCC blocker, alleviated the neurotoxicity induced by co-application of Fe SO4 and FeSO_4/CaCl_2. Further studies indicated that MPP~+ treatment accelerated the iron influx into VM neurons. In addition, FeSO_4 treatment significantly increased the intracellular Ca~(2+)concentration.These effects were blocked by isradipine. These results suggest that elevated extracellular Ca~(2+)aggravates ironinduced neurotoxicity. LTCCs mediate iron transport in dopaminergic neurons and this, in turn, results in elevated intracellular Ca~(2+)and further aggravates iron-induced neurotoxicity. |
