Contribution of KV7 Channels to Basal Coronary Flow and Active Response to Ischemia
Contribution of KV7 Channels to Basal Coronary Flow and Active Response to Ischemia
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DOI：
10.1161/hypertensionaha.113.01244
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发表时间：
2013-12-01
期刊：
影响因子：
8.3
通讯作者：
Olesen, Soren-Peter
中科院分区：
文献类型：
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作者：
Khanamiri, Saereh;Soltysinska, Ewa;Olesen, Soren-Peter
本研究的目的是确定KCNQ编码的K-v通道（K（v）7通道）在正常血压和高血压大鼠冠状动脉流量的被动和主动调节中的作用。在正常血压大鼠的冠状动脉左前降支中，结构上不同的K（v）7.2至7.5激活剂产生舒张，这在高血压大鼠的动脉中相当少，并且不被K（v）7.1特异性激活剂R-L3模仿。在离体灌注心脏标本中，冠状动脉流速对K（v）7.2至7.5激活剂（S）-1的反应增加，而在K（v）7抑制剂存在下减少。定量聚合酶链反应测定正常和高血压大鼠冠状动脉中KCNQ 1 -5及其已知辅助KCNE 1 -5亚基的表达水平相似。然而，K（v）7.4蛋白表达在高血压大鼠减少。腺苷或A2 A受体激动剂CGS-21680的应用产生浓度依赖性舒张冠状动脉从正常血压大鼠，这是衰减的应用K（v）7抑制剂。在Langendorff研究中，K（v）7阻滞剂也减弱了缺血诱导的冠状动脉灌注增加。总的来说，这些数据建立了K（v）7通道作为冠状动脉血流在静息和缺氧损伤后的重要调节剂。
The goal of the present study was to determine the role of KCNQ-encoded K-v channels (K(v)7 channels) in the passive and active regulation of coronary flow in normotensive and hypertensive rats. In left anterior descending coronary arteries from normotensive rats, structurally different K(v)7.2 to 7.5 activators produced relaxations, which were considerably less in arteries from hypertensive rats and were not mimicked by the K(v)7.1-specific activator R-L3. In isolated, perfused heart preparations, coronary flow rate increased in response to the K(v)7.2 to 7.5 activator (S)-1 and was diminished in the presence of a K(v)7 inhibitor. The expression levels of KCNQ1-5 and their known accessory KCNE1-5 subunits in coronary arteries were similar in normotensive and hypertensive rats as measured by quantitative polymerase chain reaction. However, K(v)7.4 protein expression was reduced in hypertensive rats. Application of adenosine or A2A receptor agonist CGS-21680 produced concentration-dependent relaxations of coronary arteries from normotensive rats, which were attenuated by application of K(v)7 inhibitors. K(v)7 blockers also attenuated the ischemia-induced increase in coronary perfusion in Langendorff studies. Overall, these data establish K(v)7 channels as crucial regulators of coronary flow at resting and after hypoxic insult.