花生四烯酸敏感和机械牵张门控的双孔钾离子通道TREK-1、TREK-2和TRAAK的生理和病理功能研究

发布时间：2018-01-03 03:26

本文关键词：花生四烯酸敏感和机械牵张门控的双孔钾离子通道TREK-1、TREK-2和TRAAK的生理和病理功能研究　出处：《中国协和医科大学》2005年博士论文　论文类型：学位论文

【摘要】：双孔钾离子通道(tandem-pore-domain potassium channels，K_(2P))是近年来新发现的一大类钾离子通道，它们在结构上与传统的钾离子通道差异很大，具有独特的4次跨膜片段(M1～M4)和两个孔道结构域(P1和P2)，即4TMS／2P结构。其中TREK-1、TREK-2和TRAAK由于序列结构和调控机制的相似性成为一类(TREK)。研究发现，它们在中枢神经系统的神经元上有特异性的分布。此外，研究表明，除了在人类有表达外，它们在大小鼠中也有表达。 TREK钾离子通道电流具有自发性、电压和时间依赖性、无失活等特性。TREK钾离子通道最显著的特征在于可以被花生四烯酸等多不饱和脂肪酸和机械牵张强烈激活，而饱和脂肪酸则没有该作用。TREK类双孔钾离子通道的另外一个电生理特性在于，，它们对于经典的钾通道阻断剂如4-AP、TEA、Cs~+等不敏感。在生理情况下，TREK可以和其它的双孔钾离子通道一起产生可兴奋细胞的漏电流，影响细胞的兴奋性。 TREK钾离子通道的独特的结构特征、特异性分布及调节方式提示，它们在中枢神经系统中可能有独特的重要作用。我们的研究致力于揭示该类钾离子通道在中枢神经系统的体温调节中枢的体温调节和急性脑缺血中的作用，深入阐明它们的生理和病理作用。第一部分花生四烯酸敏感和机械牵张门控的双孔钾离子通道TREK-1在大鼠中枢体温调节中的作用
[Abstract]:Tandem-pore-domain potassium channels are a new class of potassium channels discovered in recent years. Their structures are very different from the traditional potassium channels, and they have four unique transmembrane fragments (M1M4) and two pore domains (P1 and P22). TREK-1TREK-2 and TRAAK are a kind of TREK-2 because of the similarity of sequence structure and regulatory mechanism. In addition, studies have shown that they are expressed not only in humans, but also in mice and mice. The current of TREK potassium channel is spontaneous, voltage and time dependent. The most significant feature of the Trk potassium channel is that it can be strongly activated by polyunsaturated fatty acids such as arachidonic acid and mechanical distraction. But saturated fatty acids do not have this effect. Another electrophysiological characteristic of TREK bimodal potassium channels is that they are effective against classical potassium channel blockers such as 4-APTEA. Under physiological conditions TREK can produce the leakage current of excitable cells together with other two-pore potassium channels and affect the excitability of cells. The unique structural characteristics, specific distribution and regulation mode of TREK potassium ion channels are suggested. They may play a unique role in the central nervous system. Our research has focused on revealing the role of these potassium channels in central nervous system thermoregulation and acute cerebral ischemia. Their physiological and pathological functions are elucidated in depth. The role of arachidonic acid sensitive and mechanically tension-gated two-pore potassium channel TREK-1 in central thermoregulation in rats
【学位授予单位】：中国协和医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363

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