Contribution of KV7 Channels to Basal Coronary Flow and Active Response to Ischemia

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.