From The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom (Q.A., A.M.T., Y.L., K.-E.N., L.G., A.T.); and Department of Medicine, University College London, London, United Kingdom (J.G., R.A., W.R.S., A.T.).
Hypertension. 2014 Sep;64(3):523-9. doi: 10.1161/HYPERTENSIONAHA.114.03116. Epub 2014 Jun 9.
ATP-sensitive potassium channels (KATP) regulate a range of biological activities by coupling membrane excitability to the cellular metabolic state. In particular, it has been proposed that KATP 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 KATP 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 KATP 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 KATP 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 KATP channel and has a key role in vascular reactivity and blood pressure control.
三磷酸腺苷敏感性钾通道（KATP）通过将细胞膜兴奋性与细胞代谢状态偶联，调节多种生物活性。特别是，已经提出 KATP 通道，特别是通道亚基 Kir6.1 和 SUR2B，在调节血管张力方面发挥重要作用。然而，最近的实验表明，血管平滑肌外的 KATP 通道是观察到的行为的关键决定因素。因此，我们使用一种新型的小鼠模型来解决血管平滑肌 KATP 通道的重要性，在这种模型中，可以条件性地删除 Kir6.1 亚基。我们使用分子、电生理、体外和体内技术的组合，证实了平滑肌中 Kir6.1 和 KATP 电流和反应的特异性缺失。Kir6.1 条件性缺失的小鼠在使用麦角新碱诱发后甚至没有明显的心律失常表型。然而，这些小鼠患有高血压，血管平滑肌细胞不能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 KATP 通道的基础，在血管反应性和血压控制中发挥关键作用。
