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G蛋白偶联受体调节GIRK通道的特异性研究

发布时间:2018-01-01 08:07

  本文关键词:G蛋白偶联受体调节GIRK通道的特异性研究 出处:《河北医科大学》2005年硕士论文 论文类型:学位论文


  更多相关文章: G 蛋白偶联受体 GIRK G 蛋白 Gβγ


【摘要】:G 蛋白门控的内向整流钾离子通道(G protein gated inwardly rectifying K channels, GIRK)是内向整流钾通道家族中的一员(Kir3),表达于心血管和神经组织中,它的特点是功能受G 蛋白的调节。某些G 蛋白偶联受体可通过影响其功能影响心肌细胞、神经细胞和神经内分泌细胞的兴奋性。GIRK1 和GIRK4 主要分布在心房和窦房结细胞中,在调节心脏兴奋性中起重要作用,由迷走神经释放的递质乙酰胆碱(Acetylcholine, ACh) 通过兴奋II型毒菌碱样受体(m2)以及下游的PTX 敏感的Gi 蛋白激活GIRK 通道,引起膜动作电位超极化,减少动作电位的频率,减慢心率。GIRK2 主要分布在中枢神经系统,许多神经递质如γ-氨基丁酸、多巴胺、5-羟色胺和阿片肽类等通过激活PTX 敏感的Gi 蛋白激活GIRK 通道,调节神经细胞的兴奋性。已完成的研究结果清楚地表明,GIRK 可直接被Gi 蛋白释放的Gβγ激活,是Gβγ直接的效应VP。然而正常生理条件下只有PTX 敏感的Gi 家族G 蛋白激活后可激活GIRK 通道,而PTX 不敏感的G 蛋白如Gq 和Gs 激活后却不能激活GIRK 通道。因此G蛋白调节GIRK 通道存在有特异性。虽然到目前为止已发现了5 种β亚单位和12 种γ亚单位但近来研究表明几乎所有不同组合形式的G 均能直接激活GIRK 通道,显然用不同G蛋白含有不同Gβγ的组合类型不能解释G 蛋白调节GIRK通道的特异性。在本实验中,以非洲爪蟾卵母细胞为表达系
[Abstract]:G protein gated inward rectifier potassium channel G protein gated inwardly rectifying K channels. Kirk is a member of the inward rectifier potassium channel family and is expressed in cardiovascular and neural tissues. Its function is regulated by G protein. Some G protein-coupled receptors affect cardiomyocytes by affecting its function. Excitability of nerve cells and neuroendocrine cells. GIRK1 and GIRK4 are mainly distributed in atrial and sinus node cells and play an important role in regulating cardiac excitability. Acetylcholine, a transmitter released from the vagus nerve. Ache activates the GIRK channel by stimulating the type II alkaloid receptor m2) and downstream PTX sensitive GI protein, which leads to the hyperpolarization of the membrane action potential. Reduce the frequency of action potential, slow down heart rate. GIRK2 mainly distributed in the central nervous system, many neurotransmitters such as gamma-aminobutyric acid, dopamine. 5-hydroxytryptamine and opioid peptides regulate the excitability of nerve cells by activating GIRK channels by activating the PTX sensitive GI protein. GIRK was directly activated by G 尾 纬 released by GI protein. However, under normal physiological conditions, only G protein of PTX sensitive GI family can activate GIRK channel. However, G proteins that are not sensitive to PTX, such as GQ and Gs, can not activate GIRK channel after activation. Therefore, G protein regulates GIRK. Although five 尾 subunits and 12 纬 subunits have been identified so far, recent studies have shown that almost all combinations of G can directly activate GIRK channels. Obviously, different G protein combinations containing different G 尾 纬 could not explain the specificity of G protein in regulating GIRK channels. In this study, Xenopus laevis oocytes were used as expression lines.
【学位授予单位】:河北医科大学
【学位级别】:硕士
【学位授予年份】:2005
【分类号】:R33


本文编号:1363629

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