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

Sung Eun Kim; Ming Zhe Yin; Hae Jin Kim; Rany Vorn; Hae Young Yoo; Sung Joon Kim

doi:10.4196/kjpp.2020.24.1.111

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

Korean J Physiol Pharmacol. 2020 Jan;24(1):111-119. doi: 10.4196/kjpp.2020.24.1.111. Epub 2020 Dec 20.

Authors

Sung Eun Kim^{1

2}, Ming Zhe Yin^{1

2}, Hae Jin Kim^{1

2}, Rany Vorn³, Hae Young Yoo³, Sung Joon Kim^{1

2

4}

Affiliations

¹ Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea.
² Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
³ Department of Nursing, Chung-Ang University, Seoul 06974, Korea.
⁴ Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.

Abstract

In vascular smooth muscle, K⁺ channels, such as voltage-gated K⁺ channels (Kv), inward-rectifier K⁺ channels (Kir), and big-conductance Ca²⁺-activated K⁺ channels (BK_Ca), 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 (LCSMCs), 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 LCSMCs, (2) I_Kv inactivation occurred at more negative voltages in SCSMCs than those in RCSMCs and LCSMCs, (3) I_Kir was smaller in SCSMCs than that in RCSMCs and LCSMCs, 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 I_Kir 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.

Keywords: Coronary artery; Inward rectifier K+ channel; Potassium channel; Pulmonary arterial hypertension; Smooth muscle.