Work

Functional Kir2 and Katp Channels in Human Pulmonary Vascular Smooth Muscle and Endothelium Modulate Arterial Tone

Year: 2026

Type: article

Abstract: The resting membrane potential (V M ) of vascular cells is a major determinant of arterial tone, integrating the activity of multiple ionic conductances. In human pulmonary arteries, however, the specific K + channels that establish V M in smooth muscle and endothelial cells remain poorly characterized. Freshly isolated human pulmonary arterial smooth muscle (PASMCs) and endothelial cells (PAECs) were studied using whole-cell patch-clamp electrophysiology, immunofluorescence, and wire myography. Kir2 currents were assessed using Ba 2+ , whereas K ATP activity was evaluated with the synthetic activator pinacidil and the specific blockers glibenclamide and PNU-37883A. Concentration–response effects were examined in intact pulmonary artery rings. Ba 2+ -sensitive, strongly inwardly rectifying currents were identified in both PASMCs and PAECs, consistent with Kir2.1/2.2 expression. In intact arteries, BaCl 2 induced concentration-dependent contractions and attenuated acetylcholine-evoked, endothelium-dependent relaxation, indicating a tonic vasodilatory influence of Kir2 channels. Pinacidil activated glibenclamide or PNU-sensitive K ATP currents and produced vasodilation in isolated arteries, effects that were bunted by glibenclamide or PNU-37883A pretreatment. Robust Kir6.1 and SUR2 immunoreactivity further supported the presence of functional K ATP channels. This study provides the first electrophysiological evidence for native Kir2 and K ATP channels in human pulmonary vascular cells and demonstrates their contribution to arterial tone, highlighting these channels as potential therapeutic targets in pulmonary vascular disease.

Source: Open Respiratory Archives

DOI: 10.1016/j.opresp.2026.100560