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Study on the diversity of the cardiac inward rectifier potassium channels

心脏内向整流钾通道多样性的研究

基本信息

批准号：
12670042
负责人：
YANAGI(ISHIHARA)
金额：
$ 1.73万
依托单位：
Saga Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670042/
关键词：
Potassium channel Inward rectifier potassium current Cardiac myocyte

项目摘要

The inward rectifier potassium (Kir) channels play an important role in maintaining the resting potential, promoting the repolarization of action potentials and controlling the cell excitability in cardiac myocytes. Kir genes in the subgroup Kir2 encode the a subunits of Kir channels that display the properties of the strong inward rectifier I_<K1> in cardiac myocytes. To explore the significance of different Kir channels in the cardiac function, we studied the electrophysiological properties of the Kir2.1 and Kir2.2 channels of the mouse and human by heterologously expressing them in mammalian cells. We found that Kir2.1 and Kir2.2 channels showed different sensitivities to the blockage by intracellular polyamines and Mg^<2+>, which function as the intrinsic Kir channel blockers. The results suggested that Kir2.1 channel underlies I_<K1> in cardiac myocytes at physiological cytoplasmic conditions. We also studied the function of the human Kir2.1 and Kir2.2 genes cloned from healthy individuals, and found a variance in the Kir2.2 gene, which caused a functional loss of the channel.

内向整流钾通道（Kir）在维持心肌细胞静息电位、促进动作电位复极和控制细胞兴奋性等方面发挥重要作用。Kir2亚群中的Kir基因编码Kir通道的α亚基，其在心肌细胞中显示强内向整流I_2的特性<K1>。为了探讨不同的Kir通道在心脏功能中的意义，我们通过在哺乳动物细胞中异源表达小鼠和人的Kir2.1和Kir2.2通道来研究它们的电生理特性。我们发现，Kir2.1和Kir2.2通道对细胞内多胺和Mg^<2+>的阻断表现出不同的敏感性，这两种物质都是Kir通道的内源性阻断剂。结果提示，<K1>在生理性细胞质条件下，Kir2.1通道是心肌细胞I_2的基础。我们还研究了从健康个体克隆的人Kir2.1和Kir2.2基因的功能，发现Kir2.2基因的变异导致通道功能丧失。