权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Regulation of ATP-sensitive K^+ channel gene expression in myocardial ischemia

心肌缺血中 ATP 敏感 K^ 通道基因表达的调节

基本信息

批准号：
09670713
负责人：
MURAKAMI Tomoyuki
金额：
$ 1.98万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670713/
关键词：
Myocardial Ischemia K_<ATP> Channel Angiotensin II K_<ATP>チャネル KATP channel myocardial ischema gene expression

项目摘要

The cardiac ATP-sensitive potassium (K_<ATP>) channel is thought to be a complex composed of an inward rectifier potassium channel (Kir6.1 and/or Kir6.2) subunit and the sulfonylurea receptor (SUR2). We examined the transcriptional expression of these genes in rats with myocardial ischemia. Both 60 mm of myocardial regional ischemia followed by 24-72 h of reperfusion and 24 h of continuous ischemia without reperfusion specifically upregulated Kir6.1 mRNA not only in the ischemic (2.7-3.1-fold) but also in the non-ischemic (2.0-2.6-fo1d) region of the left ventricle. In contrast, mRNAs for Kir6.2 and SUR2 remained unchanged under these ischemic procedures. Western blotting demonstrated similar increases in the Kir6.1 protein level both in the ischemic (2.4-fold) and the non-ischemic (2.2-fold) region of rat hearts subjected to 60 mm of ischemia followed by 24 h of reperfusion. These findings suggest that humoral and/or hemodynamic factors are responsible for this delayed and specific up-regulation of Kir6.1. In the next study, pretreatment with TCV-116, an angiotensin (Ang) II type .1 receptor antagonist, completely inhibited the upregulation of Kir6.1 mRNA and protein expression in both regions of rat hearts subjected to 60 mm of coronary artery occlusion followed by 24 h of reperfusion ; whereas pretreatment with lisinopril, an Ang converting enzyme (ACE) inhibitor, partly inhibited this upregulation. In addition, except for rats pretreated with TCV-116, Kir6.1 mRNA levels were positively correlated with those for brain natriuretic peptide (BNP), a molecular indicator of regional wall stress, in both the non-ischemic and the ischemic regions. Plasma Ang II levels were not elevated in rats with control myocardial ischemia compared .with sham rats. Thus, stress-induced release of tissue Ang II regulates the specific induction of cardiac Kir6.1 mRNA and protein expression under myocardial ischemia.

心脏ATP敏感性钾<ATP>通道是由内向整流钾通道（Kir6.1和/或Kir6.2）亚单位和磺酰脲受体（SUR 2）组成的复合物。我们检测了这些基因在心肌缺血大鼠中的转录表达。60 mm心肌局部缺血后再灌注24-72 h和24 h连续缺血无再灌注均特异性上调Kir6.1 mRNA，不仅在缺血区（2.7-3.1倍），而且在非缺血区（2.0-2.6倍）。相反，Kir6.2和SUR 2的mRNA在这些缺血程序下保持不变。Western blotting表明，Kir6.1蛋白水平在缺血（2.4倍）和非缺血（2.2倍）区域的大鼠心脏缺血60毫米，然后再灌注24小时的类似增加。这些发现表明，体液和/或血液动力学因素是负责这种延迟和特异性上调Kir6.1。在接下来的研究中，预先用TCV-116（一种血管紧张素（Ang）II 1型受体拮抗剂）完全抑制了大鼠心脏两个区域Kir6.1 mRNA和蛋白表达的上调，这些大鼠心脏进行了60 mm冠状动脉闭塞，然后再灌注24 h;而预先用赖诺普利（一种血管紧张素转换酶（ACE）抑制剂）部分抑制了这种上调。此外，除了用TCV-116预处理的大鼠外，Kir6.1 mRNA水平与非缺血和缺血区域的脑钠肽（BNP）（区域壁应力的分子指标）呈正相关。与假手术组相比，对照组心肌缺血大鼠血浆Ang II水平未升高。因此，应力诱导的组织血管紧张素II的释放调节心肌缺血下心脏Kir6.1 mRNA和蛋白表达的特异性诱导。