L-type Calcium Channels are Involved in Iron-induced Neurotoxicity in Primary Cultured Ventral Mesencephalon Neurons of Rats
Yu-Yu Xu1 • Wen-Ping Wan1 • Sha Zhao1 • Ze-Gang Ma 1,2
1 Department of Physiology, School of Basic Medicine, Qingdao University, Qingdao 266071, China
2 Institute of Brain Science and Disorders, Qingdao University, Qingdao 266071, China
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.
L-type Ca2+ channels; Iron overload; Parkinson’s disease; Isradipine; Dopamine neuron