The ATP-Sensitive Potassium Channel Subunit, Kir6.1, in Vascular Smooth Muscle Plays a Major Role in Blood Pressure Control
The ATP-Sensitive Potassium Channel Subunit, Kir6.1, in Vascular Smooth Muscle Plays a Major Role in Blood Pressure Control
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DOI：
10.1161/hypertensionaha.114.03116
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发表时间：
2014-09-01
期刊：
影响因子：
8.3
通讯作者：
Tinker, Andrew
中科院分区：
文献类型：
--
作者：
Aziz, Qadeer;Thomas, Alison M.;Tinker, Andrew
ATP敏感性钾通道（K-ATP）通过将细胞膜兴奋性与细胞代谢状态耦合来调节一系列生物活动。特别地，已经提出K-ATP通道，特别是通道亚基Kir6.1和SUR 2B，在调节血管张力中起重要作用。然而，最近的实验表明，血管平滑肌室外的K-ATP通道是所观察到的行为的关键决定因素。因此，我们解决的重要性，血管平滑肌K-ATP通道，使用一种新的小鼠模型，其中有可能有条件地删除Kir6.1亚基。使用分子，电生理，体外和体内技术的组合，我们证实了Kir6.1和K-ATP电流和反应的情况下，特别是在平滑肌。Kir6.1条件性缺失的小鼠即使在用麦角新碱激发后也没有表现出明显的免疫表型。然而，这些小鼠患有高血压，血管平滑肌细胞无法以正常方式对血管扩张剂作出反应。因此，Kir6.1是血管平滑肌K-ATP通道的基础，在血管反应性和血压控制中起关键作用。
ATP-sensitive potassium channels (K-ATP) regulate a range of biological activities by coupling membrane excitability to the cellular metabolic state. In particular, it has been proposed that K-ATP channels and specifically, the channel subunits Kir6.1 and SUR2B, play an important role in the regulation of vascular tone. However, recent experiments have suggested that K-ATP channels outside the vascular smooth muscle compartment are the key determinant of the observed behavior. Thus, we address the importance of the vascular smooth muscle K-ATP channel, using a novel murine model in which it is possible to conditionally delete the Kir6.1 subunit. Using a combination of molecular, electrophysiological, in vitro, and in vivo techniques, we confirmed the absence of Kir6.1 and K-ATP currents and responses specifically in smooth muscle. Mice with conditional deletion of Kir6.1 showed no obvious arrhythmic phenotype even after provocation with ergonovine. However, these mice were hypertensive and vascular smooth muscle cells failed to respond to vasodilators in a normal fashion. Thus, Kir6.1 underlies the vascular smooth muscle K-ATP channel and has a key role in vascular reactivity and blood pressure control.