L-type Calcium Channels are Involved in Iron-induced Neurotoxicity in Primary Cultured Ventral Mesencephalon Neurons of Rats.

In the present study, we investigated the mechanisms underlying the mediation of iron transport by L-type Ca channels (LTCCs) in primary cultured ventral mesencephalon (VM) neurons from rats. We found that co-treatment with 100 µmol/L FeSO 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 µmol/L CaCl further aggravated the FeSO-induced neurotoxicity in MPP-treated VM neurons. Co-treatment with 10 µmol/L isradipine, an LTCC blocker, alleviated the neurotoxicity induced by co-application of FeSO and FeSO/CaCl. Further studies indicated that MPP treatment accelerated the iron influx into VM neurons. In addition, FeSO treatment significantly increased the intracellular Ca concentration. These effects were blocked by isradipine. These results suggest that elevated extracellular Ca aggravates iron-induced neurotoxicity. LTCCs mediate iron transport in dopaminergic neurons and this, in turn, results in elevated intracellular Ca and further aggravates iron-induced neurotoxicity.