Mice lacking sulfonylurea receptor 2 (SUR2) ATP-sensitive potassium channels are resistant to acute cardiovascular stress
Mice lacking sulfonylurea receptor 2 (SUR2) ATP-sensitive potassium channels are resistant to acute cardiovascular stress
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DOI：
10.1016/j.yjmcc.2007.07.058
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发表时间：
2007-10-01
影响因子：
5
通讯作者：
McNally, Elizabeth M.
中科院分区：
文献类型：
--
作者：
Stoller, Douglas;Kakkar, Rahul;McNally, Elizabeth M.
三磷酸腺苷敏感钾（K-ATP）通道被认为通过感应细胞内ATP浓度介导应激反应。心肌细胞K-ATP通道由成孔的Kir6.2亚基和调节性磺酰脲受体2 （SUR2）组成。我们研究了SUR2缺失小鼠对急性异丙肾上腺素的反应，作为急性肾上腺素能应激的模型，发现SUR2缺失小鼠在基线时观察到的发作性冠状动脉痉挛得到了缓解。类似的结果被观察到后给予一氧化氮供体一致的血管扩张作用。langendorff灌注的心脏遭受全局缺血，与对照组小鼠相比，SUR2缺失小鼠的心脏表现出明显减少的梗死面积（54 +/- 4%对30 +/- 3%）和改善的心功能。SUR2缺失小鼠出现高血压并发生心肌肥厚。然而，尽管长期存在高血压，但在SUR2缺失的小鼠中没有纤维化。SUR2无效小鼠给予硝苯地平阻断基线冠状血管痉挛，硝苯地平治疗的SUR2无效小鼠的心脏与未治疗的SUR2无效小鼠相比，梗死面积增加（42 +/- 3%对54 +/- 3%）。我们得出结论，传统的含有全长SUR2的肌层心肌细胞K-ATP通道不需要介导急性心血管应激反应。(C) 2007爱思唯尔公司版权所有。
Adenosine triphosphate-sensitive potassium (K-ATP) channels are thought to mediate the stress response by sensing intracellular ATP concentration. Cardiomyocyte K-ATP channels are composed of the pore-forming Kir6.2 subunit and the regulatory sulfonylurea receptor 2 (SUR2). We studied the response to acute isoproterenol in SUR2 null mice as a model of acute adrenergic stress and found that the episodic coronary vasospasm observed at baseline in SUR2 null mice was alleviated. Similar results were observed following administration of a nitric oxide donor consistent with a vasodilatory role. Langendorff-perfused hearts were subjected to global ischemia, and hearts from SUR2 null mice exhibited significantly reduced infarct size (54 +/- 4 versus 30 +/- 3%) and improved cardiac function compared to control mice. SUR2 null mice have hypertension and develop cardiac hypertrophy. However, despite longstanding hypertension, fibrosis was absent in SUR2 null mice. SUR2 null mice were administered nifedipine to block baseline coronary vasospasm, and hearts from nifedipine-treated SUR2 null mice exhibited increased infarct size compared to untreated SUR2 null mice (42 +/- 3% versus 54 +/- 3%). We conclude that conventional sarcolemmal cardiomyocyte K-ATP channels containing full-length SUR2 are not required for mediating the response to acute cardiovascular stress. (C) 2007 Elsevier Inc. All rights reserved.