钾离子通道的钡离子阻断机制的研究

发布时间：2018-04-12 15:56

本文选题：钾离子通道 + 离子选择筛　；参考：《浙江大学》2016年博士论文

【摘要】：钾离子通道能够控制钾离子选择性地并且高速地流入和流出细胞来改变细胞内外电压,从而使得细胞对外界刺激产生瞬间反应。钾离子通道的离子选择筛中的四个钾离子结合位点只能同时容纳两个钾离子,钾离子在离子选择筛中以1,3和2,4两种相互平衡的状态存在。钡离子是唯一一个能够阻断钾离子通道的碱土金属元素,钡离子和钾离子大小类似(钡的离子半径为1.35A,钾为1.33 A),然而钡离子却携带双倍的电荷。钡离子的大小使得它很容易进入钾离子通道的离子选择筛,然而它所携带的电荷使它在离子选择筛中的结合过于紧密,因而导致钡离子对钾离子通道的阻断效应。离子通道研究领域的先驱,布兰迪斯大学(Brandeis University)的Christopher Miller博士在上世纪八十年代通过对钾通道的钡阻断进行电生理学研究发现钾离子对于钡离子从钾通道逃逸存在三个效应：外部锁定效应(external lock-in effect)、增强效应(enhancement effect)和内部锁定效应(internal lock-in effect),他还前瞻性地推理出钾离子通道的结构,并在十几年后被钾离子通道的晶体结构所验证。然而钡离子和钾离子在钾离子通道中是如何相互作用而导致这些效应,至今仍然是离子通道研究领域争议的热点。我们以MthK钾离子通道为模型,通过多学科交叉,结合X-射线晶体学和电生理学两种研究手段,探讨了钡离子和钾离子在MthK钾离子通道内的相互作用,对上述三个效应提出了一个相应的模型。在没有钡离子时,钾离子在钾离子通道的离子选择筛中以1,3-和2,4-两种相互平衡的状态存在,此时,钾离子通道能够自由通透钾离子。钡离子从胞内侧进入钾离子通道离子选择筛,结合在4、3或2位点阻断钾离子通道。钡离子可以向外或向内逃逸出使钾离子通道畅通。钾离子从外侧进入位点1,将钡离子推至位点4,阻止钡离子向外逃逸(外部锁定效应)；外侧钾离子浓度高时能将钾离子推至位点2,从而增强钡离子向内逃逸(增强效应)；内侧的钾离子在中央空穴能阻止钡离子向内逃逸(内部锁定效应)。
[Abstract]:Potassium channels can control the selective and high speed flow of potassium ions into and out of cells to change the voltage inside and outside the cells, which makes the cells react to external stimuli.The four potassium binding sites in the ion selective sieve of potassium channel can only contain two potassium ions at the same time.Barium ion is the only alkali earth metal element that can block potassium ion channel. The size of barium ion and potassium ion is similar (the radius of barium ion is 1.35A, potassium is 1.33An, but barium ion carries double charge.The size of barium ion makes it easy to enter the ion selective screen of potassium channel. However, the charge it carries makes it bind too closely in the ion selection screen, which leads to the blocking effect of barium ion on potassium channel.A pioneer in the field of ion channel research,In the 1980s, Dr Christopher Miller of Brandys University at Brandeis University conducted an electrophysiological study of the blocking of potassium channels and found that there were three effects of potassium ions on the escape of barium ions from potassium channels: external locking effect and external lock-in effect.Internal lock-in effectts and internal locking effects. He also extrapolated the structure of potassium channels in a forward-looking way.The crystal structure of potassium channel was verified after more than ten years.However, how barium ion and potassium ion interact in potassium channel and lead to these effects is still a hot topic in the field of ion channel research.The interaction of barium ion and potassium ion in the potassium channel of MthK was studied by using the MthK potassium channel as a model, and by combining with X- ray crystallography and electrophysiology, the interaction of barium ion and potassium ion in the MthK potassium channel was studied.A corresponding model is proposed for the above three effects.In the absence of barium ion, potassium ions exist in the ion selective sieve of potassium channel in two equilibrium states of 1 ~ 3- and 2 ~ 4-. At this time, the potassium ion channel can permeate potassium ion freely.Barium ions enter the potassium channel from the medial side of the cell and block the potassium channel at 4 ~ 3 or 2 sites.Barium ions can escape outward or inward to make potassium channels clear.Potassium ions enter site 1 from the outside and push barium ions to site 4 to prevent barium ions from escaping outward (external locking effect), and potassium ions can be pushed to site 2 when the concentration of potassium ions outside is high, thus enhancing the inward escape of barium ions.The medial potassium ions in the central hole can prevent the barium ions from escaping inward.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：Q25

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