【摘 要】
：
In Parkinsons disease(PD),dopaminergic neurons in the substantia nigra(SN)are selectively degenerated,while those in the neighboring ventral tegmental area(VTA)are spared.Characteristics of ATP-sensit
【机 构】
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Department of Physiology,Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurol
【出 处】
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第九届海内外华人神经科学家研讨会(The 9th Symposium for Chinese Neuroscientis
论文部分内容阅读
In Parkinsons disease(PD),dopaminergic neurons in the substantia nigra(SN)are selectively degenerated,while those in the neighboring ventral tegmental area(VTA)are spared.Characteristics of ATP-sensitive potassium channels in the SN and nigral iron accumulation might be responsible for this selective neurodegeneration in PD.However,the relationship between ATPsensitive potassium channels and iron transportation is largely unknown.In the present study,we aim to elucidate their interaction and underlying mechanisms.When treated with ATP-sensitive potassium(KATP)channel opener,diazoxide,membrane hyperpolarization and increased iron influx could be observed in SK-N-SH cells.This resulted in an increased intracellular iron levels and subsequent decreased mitochondrial membrane potential(ΔΨm)and increased ROS production.After knockdown of the divalent metal transporter 1(DMT1),this increased iron influx was dramatically blocked.Blockage of the KATP channels with glibenclamide could protect the cells against Fe2+toxicity by partially restoring the ΔΨm,increasing the level of Cu–Zn superoxide dismutase(Cu/Zn–SOD).These results suggest that the activation of the KATP channels could enhance DMT1-mediated ferrous iron influx,resulting in the increased oxidative stress and ultimate cell damage.This might provide a new theoretical and experimental evidence for the role of KATP channels in iron accumulation and the selective degeneration in dopaminergic neurons in PD.
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