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Structure and function of mitochondrial ATP-sensitive K^+ channel.

线粒体 ATP 敏感 K^ 通道的结构和功能。

基本信息

批准号：
11670080
负责人：
GONOI Tohru
金额：
$ 2.43万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670080/
关键词：
ATP-sensitive K^+ Channel Mitochondria Kir6.1 Kir6.2 SUR1 SUR2 Jurkat cell cAMP-dependent protein kinase ATP感受性K^+チャネル代謝パッチクランプ法 Kir6.2

项目摘要

ATP-sensitive K^+ (K_<ATP>) channels open and close depending on ATP concentration in the cytoplasm, and control excitability of the cells. We have previously shown that K_<ATP> channel of pancreatic β-cell comprises SUR1, a member of ABC protein, and Kir6.2, a member of inward rectifier K channels. In heart and skeletal muscles, and blood vessels, K_<ATP> channels of similar properties comprise SUR2A/B and Kir6.x, regulating muscle contraction during hypoxia or ischemia.Although similar K_<ATP> channel is expressed in mitochondria, and regulating energy metabolism, its constituting molecules are unknown.Using the patch-clamp technique, we recorded ion channel activity from the mitochondrial inner membrane of Jurkat cells. K^+ ion selective channels with conductance of 55 pS were observed, of which activity being suppressed by 2 mM ATP.These properties and burst kinetics are similar to the channel comprising Kir6.1 molecule. In other to study if Kir6.1 molecules are induced during hypo … More xia, A7r5 cells, derived from blood vessel were cultured in medium containing Co^<2+> ions, mimicking hypoxic conditions. Western blotting using anti Kir6.1 antibody revealed that Kir6.1 protein became expressed in 3-4 days after an addition of the ions. However, no activity of channels comprising activity Kir6.1 was observed in the plasma membrane of heart of blood vessel muscles. Following these results, a possibility that Kir6.1 molecule induced in ischemia composes mitochondrial K_<ATP> channel is currently investigated.In other series of experiments effects of protein kinase A mediated phosphorylation of K_<ATP> channels comprising SUR1 and Kir6.2 were studied. We found both subunits are phosphorylated and channel properties are modulated in a different manner.Finally, effects of anti-diabetic reagents, troglitazone, pioglitazone, and KAD-1229, were studied on reconstituted K_<ATP> channels. The studies are helpful in understanding structure-function relationship of K_<ATP> channels in the plasma membrane as well as mitochondria. Less

ATP敏感性K^+（K_<ATP>）通道依赖于细胞质中ATP浓度的变化而开放和关闭，并控制细胞的兴奋性。胰腺<ATP>β细胞钾通道由ABC蛋白SUR 1和内向整流钾通道Kir6.2组成。在心肌、骨骼肌和血管中，<ATP>具有相似特性的K_通道包括SUR 2A/B和Kir6.x，它们在缺氧或缺血时调节肌肉收缩，虽然类似的K_<ATP>通道在线粒体中表达，并调节能量代谢，但其组成分子尚不清楚。结果表明，K^+离子选择性通道的电导率为55 pS，其活性可被2 mM ATP抑制，这些特性和爆发动力学与Kir6.1分子组成的通道相似。在另一项研究中，如果Kir6.1分子在低血糖期间被诱导， ...更多信息将来源于血管的A7 r5细胞在含有Co^2+离子的培养基中培养，模拟缺氧条件。用抗Kir6.1抗体进行的Western blotting显示，Kir6.1蛋白在加入离子后3-4天开始表达。然而，在血管肌肉的心脏的质膜中没有观察到包含活性Kir6.1的通道的活性。在此基础上，进一步探讨了缺血诱导的Kir6.1分子参与线粒体K_通道的可能性<ATP>，并进一步研究了蛋白激酶A（PKA）介导的K_2通道磷酸化的作用<ATP>。最后，研究了抗糖尿病药物曲格列酮、吡格列酮和KAD-1229对重构钾通道的影响<ATP>。这些研究有助于理解质膜和线粒体K通道的结构与功能关系<ATP>。少