文档介绍：l|III I I Ill Ul 1 11 II II IIIl
Y1 90 1 440
目 录
中文摘要 O O O O O O A O O O O O 1
英文摘要 8
英文缩写 15
研究论文 Q2/3通道作用的构效关系与机制研究
引言”..““一”“ ..“..“”””“””一”..”“一 ”“””“·16 Q2/3钾离子通道电流的鉴定
前言·······················日IJ吾“一“”“““”“””“一“””“””””“················· ···“·············””””一·‘18”“”“””””“一””“”萏
材料与方法 O O B O O O O O O 19
结果··· ········ ······· ·······“············..”””..一“”””““”·25 附图 29
讨论········ ············· ·?············-················· ·············37 小结-········ ····· 一············ “““········?””··”····· “”38 参考文献 38
第二部分Structure—activity relationship study of PPO derivatives
on KCNQ2/3 currents
前言月IJ舌““””””“一”””“”“””一”··· ······ ······ ···O O O O O O”””””··· 一“”””一”““””。42······ 42
材料与方法 43
结果 · ··············-·--········ ····················· ········· 47 附l訇··············································································49 附表”一”””””一”“””“一“”””“”””““””””一“一“···”一“““·59
讨论”””···“““““””””””””..”一“”“”“””““”””·“一..”””62
小结”““”··”“··”..””·””“““..”””“一···一”·”“········“·””····64 参考文献 64
第三部分Characteristics and mechanism for the effects of PPO derivatives activation of KCNQ2/3 currents
前言日U舌”““””“”。O OO O O O”一””“”“”””一”“”““”””””“““””“”.6868
材料与方法 69
结果··· ··· ············· ·· ······ -·· ······ ··· 73
·········································78
····················-····················94
··”·”····”·······”···”· ·······98
··”··”-······”···mo o·“·-”· 一···”99
········”····”········..···”·····”100
·········································102
··”··”·”·“····””· “·”·”····”·103
······--·····························-···124
·········································141
··“·····””··”···”·“······”·”“···142
中文摘要
Q2/3通道作用的构效关系
与机制研究
摘 要
M电流是由Brown及Adams于1980年首次在牛蛙颈上交感神经节中发现的一种具有电压依赖性、慢激活、非失活、慢去活等特征的外向钾电流。由于这种外向钾电流可被M型受体激动剂毒蕈碱(Muscarine)强烈抑制,因而得名为M电流,其离子通道称为M通道。Q家族成员()构成的同源四聚体或异四聚体是构成M通道的分子基础。以 KCNQ为分子基础的M电流对于维持和稳定神经元的兴奋性发挥着重要作用。M电流被抑制后,细胞膜发生去极化,使膜电位更接近阈电位,细胞更易爆发动作电位,神经元的兴奋性增加。研究发现,Q3 基因突变可诱发由于神经元过度兴奋所致的家族遗传性新生儿惊厥症(benign familial