Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1
Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1
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DOI：
10.1038/nm0502-466
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发表时间：
2002-05-01
期刊：
影响因子：
82.9
通讯作者：
Seino, S
中科院分区：
文献类型：
--
作者：
Miki, T;Suzuki, M;Seino, S
在重构的体系中，向内整流的K+通道Kir6.1通过与磺酰脲受体偶联形成K+通道，但含有Kir6.1的K+通道的生理作用尚未确定。我们在此报告，缺乏Kir6.1（称为Kcnj8）基因编码的小鼠在心电图上显示，与自发性ST段抬高相关的猝死率很高，随后出现房室传导阻滞。K+通道开启剂pinacidil不会在kir6.1缺失小鼠血管平滑肌细胞中诱导K+电流，pinacidil对血管无舒张反应。甲麦角新碱是一种血管收缩剂，在kir6.1缺失小鼠中引起ST段抬高，随后心脏死亡，但在野生型小鼠中没有，这表明一种以冠状动脉过度收缩为特征的表型，类似于人类的Prinzmetal（或变异性）心绞痛。含有kir6.1的K+通道对血管张力的调节至关重要，特别是在冠状动脉中，它的破坏可能导致Prinzmetal心绞痛。
The inwardly rectifying K+ channel Kir6.1 forms K+ channels by coupling with a sulfonylurea receptor in reconstituted systems, but the physiological roles of Kir6.1-containing K+ channels have not been determined. We report here that mice lacking the gene encoding Kir6.1 (known as Kcnj8) have a high rate of sudden death associated with spontaneous ST elevation followed by atrioventricular block as seen on an electrocardiogram. The K+ channel opener pinacidil did not induce K+ currents in vascular smooth-muscle cells of Kir6.1-null mice, and there was no vasodilation response to pinacidil. The administration of methylergometrine, a vasoconstrictive agent, elicited ST elevation followed by cardiac death in Kir6.1-null mice but not in wild-type mice, indicating a phenotype characterized by hypercontractility of coronary arteries and resembling Prinzmetal (or variant) angina in humans. The Kir6.1-containing K+ channel is critical in the regulation of vascular tonus, especially in the coronary arteries, and its disruption may cause Prinzmetal angina.