Decreased inward rectifier and voltage-gated K+ currents of the right septal coronary artery smooth muscle cells in pulmonary arterial hypertensive rats

Abstract

In vascular smooth muscle, K+ channels, such as voltage-gated K+ channels (K-v), inward-rectifier K+ channels (Kir), and big-conductance Ca2+-activated K+ channels (BKca), establish a hyperpolarized membrane potential and counterbalance the depolarizing vasoactive stimuli. Additionally, Kir mediates endothelium-dependent hyperpolarization and the active hyperemia response in various vessels, including the coronary artery. Pulmonary arterial hypertension (PAH) induces right ventricular hypertrophy (RVH), thereby elevating the risk of ischemia and right heart failure. Here, using the whole-cell patch-clamp technique, we compared Kv and Kir current densities (I-kv, and I-kir) in the left (LCSMC5), right (RCSMCs), and septal branches of coronary smooth muscle cells (SCSMCs) from control and monocrotaline (MCT)-induced PAH rats exhibiting RVH. In control rats, (1) I-kv was larger in RCSMCs than that in SCSMCs and LCSMC5, (2) I-kv inactivation occurred at more negative voltages in SCSMCs than those in RCSMCs and LCSMC5, (3) I-kir was smaller in SCSMCs than that in RCSMCs and LCSMC5, and (4) I-BKCa did not differ between branches. Moreover, in PAH rats, I(kir )and I-kv decreased in SCSMCs, but not in RCSMCs or LCSMCs, and I-BKCa did not change in any of the branches. These results demonstrated that SCSMC-specific decreases in I-kv and Ikir occur in an MCT-induced PAH model, thereby offering insights into the potential pathophysiological implications of coronary blood flow regulation in right heart disease. Furthermore, the relatively smaller I-kir in SCSMCs suggested a less effective vasodilatory response in the septal region to the moderate increase in extracellular K+ concentration under increased activity of the myocardium.