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

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-4phenylpyridinium) 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 FeSO 4 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.

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