G蛋白门控内向整流钾离子通道4基因突变与原发性醛固酮增多症相关性的研究

项目名称： G蛋白门控内向整流钾离子通道4基因突变与原发性醛固酮增多症相关性的研究

项目编号： No.81460078

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 胡君丽

作者单位： 新疆维吾尔自治区人民医院

项目金额： 45万元

中文摘要： G蛋白偶联的内向整流型钾离子通道4 （GIRK4）基因突变与原发性醛固酮增多症密切相关。新疆高血压研究所发现GIRK4基因新的突变位点X2在46例肾上腺腺瘤中100%突变，制备点突变转染细胞，检测细胞的增殖效应，检测K+、Na+和Ca2+离子单通道的特性来了解X2位点突变对GIRK4通道的影响。了解其离子通道一般电学性质和动力学特性，并利用钾通道阻滞剂BaCl2、tertiapin-Q(TPN-Q)了解离子通道的调控关系；采用RT-PCR法对细胞钙调蛋白进行转录水平的测定；利用钙离子测定与成像技术对细胞内Ca2+浓度进行实时监控；采用RT-PCR法对细胞内CYP11B2基因水平进行测定，了解细胞合成分泌醛固酮的能力，与细胞增殖之间的关系，通过了解X2位点突变带来的电生理特性的改变来了解GIRK4的功能学改变，从而揭示GIRK4在原醛症中的发病机制。

中文关键词： G蛋白门控内向整流钾离子通道4；基因突变；原发性醛固酮增多症

英文摘要： G-protein coupled potassium(K+) channel 4 (GIRK4) gene mutations are closely associated with primary aldosteronism. Institute of Hypertension Research, People's Hospital of Xinjiang Uygur Autonomous Region found 100% new mutations of X2 loci of GIRK4 gene in 46 cases with adrenal adenoma, and introduced the mutated genes into 293-T cells by stable transfection. Patch clamp detection was used to detect K+, Na+ and Ca2+ ion characteristics of GIRK4 to comprehend effects of X2 mutant loci on GIRK4 ion channel. In order to explain pathogenesis of GIRK4 in primary aldosteronism, we should understand the general electrical properties and dynamic characteristics of ion channel; understand the function of ion channel regulation using potassium channel blockers BaCl2, and tertiapin-Q (TPN-Q); determine calmodulin level by RT-PCR; detect intracellular Ca2+ concentration bycalcium determination and imaging technology; and evaluate CYP11B2 gene using RT-PCR to understand relationship between the second messenger and the cell proliferation. And in order to reveal pathogenesis of GIRK4 in primary aldosteronism, we should understand changes of electrophysiological characteristics caused by X2 mutation.

英文关键词： GIRK4;Gene mutation;Primary aldosteronism