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

作　　者：Yu-Yu Xu Wen-Ping Wan Sha Zhao Ze-Gang Ma 

机构地区：[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

出　　处：《Neuroscience Bulletin》2020年第2期165-173,共9页神经科学通报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(81671249);the Natural Science Foundation of Shandong Province,China(ZR2016CM04).

摘　　要：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 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 lmol/L CaCl2 further aggravated the FeSO4-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 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 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.

关 键 词：L-type Ca^2+channels Iron overload Parkinson’s disease ISRADIPINE Dopamine neuron 

分 类 号：R742.5[医药卫生—神经病学与精神病学]