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目的帕金森氏病(PD)的主要病理表现为中脑黑质致密部多巴胺能神经元的进行性死亡,为了揭示帕金森氏病中多巴胺能神经元死亡的机制,我们研究了钾离子通道在MPP+(1-甲基-4-苯基吡啶)诱导的野生型及α-synuclein转基因SH-SY5Y细胞死亡中的作用。方法MPP+孵育野生型及转染A53T突变型α-synuclein基因的SH-SY5Y细胞,或提前孵育钾离子通道抑制剂,全细胞膜片钳技术观察钾电流的改变。结果①MPP+可以诱导野生型及转染α-synuclein基因的SH-SY5Y细胞中延迟整流钾电流[IK(DR)]的增加,并且在α-synuclein转基因细胞中IK(DR)的增加更显著;②MPP+孵育野生型及转染α-synuclein的SH-SY5Y细胞6h即可诱导Ik电流的增加,24~48h Ik电流增加加剧;③四乙铵(TEA)可以抑制MPP+诱导的野生型和α-synuclein转基因SH-SY5Y细胞中钾电流的增加。结论钾离子通道的开放及延迟整流钾电流的增加在MPP+诱导的帕金森氏病细胞模型中发挥重要作用,为揭示PD中多巴胺能神经元的凋亡提供了新的思路。
PURPOSE Parkinson’s disease (PD) is characterized by the progressive death of dopaminergic neurons in the substantia nigra pars compacta. To elucidate the mechanism of dopaminergic neuron death in Parkinson’s disease, we investigated the effects of potassium channels on The role of MPP + (1-methyl-4-phenylpyridine) -induced wild-type and α-synuclein transgenic SH-SY5Y cell death. Methods MPP + incubated SH-SY5Y cells transfected with A53T mutant α-synuclein gene or preincubated with potassium channel inhibitor. Whole-cell patch-clamp technique was used to observe the change of potassium current. Results ①MPP + induced an increase of delayed rectifier potassium current [IK (DR)] in wild-type and α-synuclein transfected SH-SY5Y cells, and more significant increase of IK (DR) in α-synuclein transgenic cells; Incubation of wild-type and SH-SY5Y cells transfected with α-synuclein for 6 h induced an increase in Ik current and an increase in Ik current from 24 to 48 h; ③ Tetraethylammonium (TEA) inhibited MPP + -induced wild-type and α-synuclein transgene Increased Potassium Current in SH-SY5Y Cells. Conclusion The opening of potassium channel and the increase of delayed rectifier potassium current play an important role in the MPP + -induced Parkinson’s disease cell model, which provides a new idea for revealing the apoptosis of dopaminergic neurons in PD.