RT Journal Article
T1 Functional expression of inwardly rectifying and ATP-sensitive potassium channels in human pulmonary artery smooth muscle and endothelial cells.
A1 Barreira, Bianca
A1 Morales Cano, Daniel
A1 Moreno Gutiérrez, Laura
A1 de Olaiz, Beatriz
A1 Adão, Rui
A1 Cogolludo Torralba, Ángel Luis
A1 Pérez Vizcaíno, Francisco
A1 Sancho González, María
AB The resting membrane potential (V) of vascular cells is a key determinant of arterial tone, integrating multiple ionic conductances to control smooth muscle contractility and endothelial signalling. In the human pulmonary circulation, the specific K channels responsible for setting the V of smooth muscle cells (SMCs) and endothelial cells (ECs) remain incompletely defined. This study investigated whether inwardly rectifying (Kir2) and ATP-sensitive (K) K channels are functionally expressed in native human pulmonary artery (PA) SMCs and ECs and assessed their contribution to vascular tone. Combining patch-clamp electrophysiology, immunofluorescence and wire myography, we evaluated channel expression and function in freshly isolated PASMCs and PAECs, and intact PAs. Kir2 channels were identified by Ba-sensitive inward currents with a characteristic rectification profile, supported by immunolabelling of Kir2.1 and Kir2.2 subunits. Functionally, BaCl induced concentration-dependent contractions of PA rings and significantly attenuated acetylcholine-evoked, endothelium-dependent relaxation, revealing a tonic vasodilatory role for Kir2 channels. K currents, activated by pinacidil and blocked by glibenclamide and PNU-37883A, were also observed in PASMCs and PAECs, consistent with immunodetection of Kir6.1 and SUR2 subunits. In isolated PAs, pinacidil elicited concentration-dependent vasodilatation, which was significantly reduced by K channel blockade. Collectively, these findings demonstrate for the first time the functional presence of Kir2 and K channels in native human pulmonary vascular cells, and their modulatory role on V and arterial tone. These channels emerge as key electro-metabolic regulators of pulmonary vascular function and promising therapeutic targets in diseases characterized by V dysregulation, such as pulmonary arterial hypertension. KEY POINTS: Inwardly rectifying (Kir2) K channels are key regulators of the resting membrane potential (V) in different vascular cell types across multiple vascular beds, whereas ATP-sensitive (K) K channels detect changes in the metabolic state of vascular cells and translate these changes into V modulation. Despite their well-established physiological relevance, a comprehensive characterization of Kir2 and K channels in freshly isolated human pulmonary vascular cells - particularly within the endothelium - remains lacking. Our study provides compelling evidence for the functional expression of Kir2 and K channels in native human pulmonary arterial smooth muscle and endothelial cells, demonstrating their contribution to V regulation and pulmonary vascular tone at rest and in response to specific stimuli.
PB Wiley
YR 2026
FD 2026-03
LK https://hdl.handle.net/20.500.14352/134712
UL https://hdl.handle.net/20.500.14352/134712
LA eng
NO Barreira B, Morales-Cano D, Moreno L, de Olaiz B, Adão R, Cogolludo A, Perez-Vizcaino F, Sancho M. Functional expression of inwardly rectifying and ATP-sensitive potassium channels in human pulmonary artery smooth muscle and endothelial cells. J Physiol. 2026 Mar;604(5):1820-1839. doi: 10.1113/JP289445.
NO European Comission
NO Ministerio de Ciencia e Innovación (España)
NO Sociedad Española de Neumología y Cirugía Torácica (SEPAR)
NO Fundación Contra la Hipertensión Pulmonar (FCHP)
NO EU Horizon 2020 Marie Skłodowska-Curie grant. Grant Number: 847635 The Spanish Ministry of Science and Innovation. Grant Numbers: PID2023-147925OA-I00, PID2020-117939RB-I00, PID PID2019-107363RB-I00 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Grant Number: 1204-2022 Fundación Contra la Hipertensión Pulmonar (FCHP). Grant Number: FD10/21_01
DS Docta Complutense
RD 4 may 2026