Fig 6. Diagram summarizing the roles of K_v7 channels in the pig right coronary artery.

It appears that a balance between K_v7 channel activation and inhibition contributes to sculpturing the shape of histamine-induced CA contractile responses. Histamine acts on the histamine H1 receptor (H1R) expressed in CA smooth muscle cells. This results in a phospholipase C (PLC)-dependent stimulation of receptor-operated and store-operated channels (ROC/SOC) mediating cation influx that depolarizes the smooth muscle cells. In turn, smooth muscle cell depolarization activates voltage-gated Ca²⁺ channels that leads to massive Ca²⁺ influx into the smooth muscle cells with a consecutive smooth muscle contraction and further depolarization. Such stronger depolarization stimulates K_v7 activity repolarizing smooth muscles and weakening coronary artery ring contractions. Conversely, histamine-dependent inhibition of K_v7 channels via a PLC-dependent mechanism leads to an increased smooth muscle cell depolarization and strengthens ring contractions. In endothelium, bradykinin-dependent ROC/SOC activation also results in Na⁺ and Ca²⁺ influx that is driven by the gradient of these cations and negative potential inside endothelial cells. However, such cation influx depolarizes endothelial cells reducing the driving force. Activation of endothelial K_v7 channels likely enhances endothelium-dependent dilatory responses in the pig right coronary artery by maintaining more negative potential inside endothelial cells that results in greater Ca²⁺ influx known to stimulate Ca²⁺-dependent nitric oxide synthase (eNOS) causing increased NO production.