The effects of structurally disparate Kv7 activators in the rat vasculature

Kv7 voltage‐gated potassium channels, encoded by KCNQ1–5 genes, are present functionally in vascular and non‐vascular smooth muscle cells. The aim of the present study was to compare the effect of structurally different activators of Kv7.2–7.5 channels: S‐1, BMS‐204352, ICA27243 and retigabine in the rat mesenteric artery, thoracic aorta and coronary circulation. Isometric tension recording was performed on segments of mesenteric artery and thoracic aorta. In addition the coronary circulation was studied using the Langendorff heart preparation. In mesenteric arteries the Kv7 activators demonstrated EC50 values of: 1.9 μM (BMS204352), 2.5 μM (S‐1), 5.4 μM (ICA27243), and 14.3 μM (retigabine). Application of all Kv7 activators at 10 μM relaxed the thoracic aorta albeit with varying efficacies. In the isolated heart increasing concentrations of Kv7 activators produced a concentration‐dependent increase in coronary flow. This study is the first to fully characterise the effects of various Kv7 channel activators in the rat mesenteric artery, thoracic aorta and coronary artery. Work was funded by BBSRC‐CASE studentship with NeuroSearch A/S.