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                鉀通道活動抑制與載脂蛋白E4引發的經由NMDA受體的鈣超載有關
                來源: | 作者: | 發布時間:2014-4-15 15:07:20

                鉀通道活動抑制與載脂蛋白E4引發的經由NMDA受體的鈣超載有關
                秦穎1,楊力凡2,翁雨藤2,駱小莉2
                (1. 上海東方醫院,同濟大學醫學院,200092; 2. 同濟大學醫學院)
                摘要:在眾多關注載脂蛋白E的ε4 單體與阿爾茨海默病之間聯系的機制中,我們的研究關注于其與鈣穩態失調之間的關系。在急性分離的海馬神經元上,我們觀察到1) apoE4快速320 大幅度的升高神經元的胞內游離鈣離子濃度,該作用呈現劑量和時間依賴性,并不可逆轉;2) 從細胞外液中移除鈣離子,可消除apoE4引發的胞內鈣離子升高;3) nicardipine 對apoE4的升鈣作業幾乎沒有影響,而MK-801 在很大幅度上可以阻斷apoE4的作用;并且4) 鉀通道的激動劑可以抑制apoE4的升鈣作用。上述實驗結果表明,apoE4經由NMDA受體,而非L型鈣通道引發神經元的胞內鈣離子濃度升高。在此過程中,鉀通道的活動的抑制與此密切相關。
                關鍵詞:載脂蛋白E4;鈣內流;鉀通道
                中圖分類號:R338

                Potassium Channels Depression is involved in the Apolipoprotein E4 enhanced Calcium Influx via N-Methyl-D-Aspartate receptor
                Qin Ying1, Yang Lifan2, Weng Yuteng2, Luo Xiaoli2
                (1. East Hospital, Tongji University School of Medicine, 200092; 2. Tongji University School of Medicine)
                Foundations: National Nature Science Foundation of China (81200823), Specialized Research Fund for the Doctoral Program of Higher Education (20100072120052) Brief author introduction:Qin Ying (1976-), Female, PhD,Physiology. 

                 Abstract: Among many suggested mechanisms of the association between the ε4 allele of apoplipoprotein E gene (APOE) and Alzheimer’s disease (AD), the present study focused on the link of  apoE4 to Ca2+ homeostasis. On the acutely isolated hippocampal neurons, our observation showed that: 1) apoE4 increased the [Ca2+]i greatly and immediately. It was in a dose- and time- dependent manner, and irreversible; 2) removing Ca2+ from external solution abolished apoE4's effect on [Ca2+]i; 3) nicardipine showed little effect on apoE4-elicited [Ca2+]i increasing, while MK-801 almost blocked the apoE4-induced Ca2+ influx; and 4) pretreatment with K+ channel opener significantly reduced the apoE4-induced [Ca2+]i increasing. The results suggest that apoE4 increased [Ca2+]i by way of NMDA receptor channels but not L-type Ca2+ channels; and the depression of K+ channel activities was involved in this effects of apoE4.
                Key words: Apolipoprotein E4, calcium influx, potassium channel

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