Contribution of K v 7 Channels to Basal Coronary Flow and Active Response to Ischemia

Abstract

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.