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

In the present study, we investigated the mechanisms underlying the mediation of iron transport by L-type Ca²⁺ channels (LTCCs) in primary cultured ventral mesencephalon (VM) neurons from rats. We found that co-treatment with 100 µmol/L FeSO₄ 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 CaCl₂ further aggravated the FeSO₄-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 FeSO₄ and FeSO₄/CaCl₂. Further studies indicated that MPP⁺ treatment accelerated the iron influx into VM neurons. In addition, FeSO₄ treatment significantly increased the intracellular Ca²⁺ concentration. These effects were blocked by isradipine. These results suggest that elevated extracellular Ca²⁺ aggravates iron-induced neurotoxicity. LTCCs mediate iron transport in dopaminergic neurons and this, in turn, results in elevated intracellular Ca²⁺ and further aggravates iron-induced neurotoxicity.