钾通道活动抑制与载脂蛋白E4引发的经由NMDA受体的钙超载有关
秦颖1，杨力凡2，翁雨藤2，骆小莉2
（1. 上海东方医院，同济大学医学院，200092； 2. 同济大学医学院）
摘要：在众多关注载脂蛋白E的ε4 单体与阿尔茨海默病之间联系的机制中，我们的研究关注于其与钙稳态失调之间的关系。在急性分离的海马神经元上，我们观察到1) apoE4快速320 大幅度的升高神经元的胞内游离钙离子浓度，该作用呈现剂量和时间依赖性，并不可逆转；2) 从细胞外液中移除钙离子，可消除apoE4引发的胞内钙离子升高；3) nicardipine 对apoE4的升钙作业几乎没有影响，而MK-801 在很大幅度上可以阻断apoE4的作用；并且4) 钾通道的激动剂可以抑制apoE4的升钙作用。上述实验结果表明，apoE4经由NMDA受体，而非L型钙通道引发神经元的胞内钙离子浓度升高。在此过程中，钾通道的活动的抑制与此密切相关。
关键词：载脂蛋白E4；钙内流；钾通道
中图分类号：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