Functional expression of inwardly rectifying and ATP‐sensitive potassium channels in human pulmonary artery smooth muscle and endothelial cells

The resting membrane potential (VM) 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 VM of smooth muscle cells (SMCs) and endothelial cells (ECs) remain incompletely defined. This study investigated whether inwardly rectifying (Kir2) and ATP‐sensitive (KATP) 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 Ba2+‐sensitive inward currents with a characteristic rectification profile, supported by immunolabelling of Kir2.1 and Kir2.2 subunits. Functionally, BaCl2 induced concentration‐dependent contractions of PA rings and significantly attenuated acetylcholine‐evoked, endothelium‐dependent relaxation, revealing a tonic vasodilatory role for Kir2 channels. KATP 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 KATP channel blockade. Collectively, these findings demonstrate for the first time the functional presence of Kir2 and KATP channels in native human pulmonary vascular cells, and their modulatory role on VM and arterial tone. These channels emerge as key electro‐metabolic regulators of pulmonary vascular function and promising therapeutic targets in diseases characterized by VM dysregulation, such as pulmonary arterial hypertension.

• Publication year

  2026

• Venue

  Journal of Physiology

• Publication date

  2026-01-28

• Fields of study

  Medicine

• Identifiers
  DOI 10.1113/JP289445PMID 41601372PMCID PMC12953014
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Distinct Potassium Channel Types in Brain Capillary Pericytes.

  2024cited by this paper
• Pulmonary hypertension associated with diazoxide: the SUR1 paradox

  2023cited by this paper
• Physiological and pathophysiological roles of the KCNK3 potassium channel in the pulmonary circulation and the heart

  2023cited by this paper
• The Conducted Vasomotor Response and the Principles of Electrical Communication in Resistance Arteries.

  2023cited by this paper
• Involvement of SUR2/Kir6.1 channel in the physiopathology of pulmonary arterial hypertension

  2023influential reference
• Adenosine signaling activates ATP-sensitive K+ channels in endothelial cells and pericytes in CNS capillaries

  2022influential reference
• Potassium (K+) channels in the pulmonary vasculature: Implications in pulmonary hypertension Physiological, pathophysiological and pharmacological regulation.

  2021influential reference
• ATP- and voltage-dependent electro-metabolic signaling regulates blood flow in heart

  2020cited by this paper
• Mechanisms underlying selective coupling of endothelial Ca2+ signals with eNOS vs. IK/SK channels in systemic and pulmonary arteries

  2020cited by this paper
• Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types

  2018influential reference
• Calcitonin gene-related peptide hyperpolarizes mouse pulmonary artery endothelial tubes through KATP channel activation.

  2018cited by this paper
• Membrane Lipid-KIR2.x Channel Interactions Enable Hemodynamic Sensing in Cerebral Arteries

  2018influential reference
• The Conducted Vasomotor Response: Function, Biophysical Basis, and Pharmacological Control.

  2018cited by this paper
• Capillary K+-sensing initiates retrograde hyperpolarization to locally increase cerebral blood flow

  2017cited by this paper
• Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.

  2017cited by this paper
• Inwardly rectifying K+ channels are major contributors to flow‐induced vasodilatation in resistance arteries

  2017cited by this paper
• Inward rectifier potassium (Kir2.1) channels as end‐stage boosters of endothelium‐dependent vasodilators

  2016influential reference
• Potassium Channel Subfamily K Member 3 (KCNK3) Contributes to the Development of Pulmonary Arterial Hypertension

  2016influential reference
• Role of acid sphingomyelinase and IL-6 as mediators of endotoxin-induced pulmonary vascular dysfunction

  2016cited by this paper
• A patient with Cantú syndrome associated with fatal bronchopulmonary dysplasia and pulmonary hypertension

  2014cited by this paper
• Hypotension Due to Kir6.1 Gain‐of‐Function in Vascular Smooth Muscle

  2013cited by this paper
• Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function

  2012cited by this paper
• Hypoxic pulmonary vasoconstriction.

  2012cited by this paper
• Endothelial and smooth muscle cell ion channels in pulmonary vasoconstriction and vascular remodeling.

  2011cited by this paper
• Determinants of pulmonary blood flow distribution.

  2010cited by this paper
• Organ culture mimics the effects of hypoxia on membrane potential, K+ channels and vessel tone in pulmonary artery

  2009cited by this paper
• Activation of neutral sphingomyelinase is involved in acute hypoxic pulmonary vasoconstriction

  2008cited by this paper
• Rho Kinase-Mediated Vasoconstriction Is Important in Severe Occlusive Pulmonary Arterial Hypertension in Rats

  2007cited by this paper
• Functional Expression of Inward Rectifier Potassium Channels in Cultured Human Pulmonary Smooth Muscle Cells: Evidence for a Major Role of Kir2.4 Subunits

  2006cited by this paper
• Glibenclamide Reveals Role for Endothelin in Hypoxia-Induced Vasoconstriction in Rat Intrapulmonary Arteries

  2005cited by this paper
• Potassium Channels in the Peripheral Microcirculation

  2005cited by this paper
• Shear stress increases expression of a KATP channel in rat and bovine pulmonary vascular endothelial cells.

  2003cited by this paper
• Functional ion channels in human pulmonary artery smooth muscle cells: Voltage-dependent cation channels

  2002cited by this paper
• The molecular composition of K(ATP) channels in human pulmonary artery smooth muscle cells and their modulation by growth.

  2002cited by this paper
• Inhibition of inwardly rectifying K(+) channels by cGMP in pulmonary vascular endothelial cells.

  2002cited by this paper
• Sustained membrane depolarization and pulmonary artery smooth muscle cell proliferation.

  2000influential reference
• Role of wall tension in hypoxic responses of isolated rat pulmonary arteries.

  1998cited by this paper
• Nitric oxide and endothelin-1 in pulmonary hypertension.

  1998cited by this paper
• Dysfunctional voltage-gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension.

  1998cited by this paper
• Resting potentials and potassium currents during development of pulmonary artery smooth muscle cells.

  1998cited by this paper
• Role of wall tension in hypoxic responses of isolated rat pulmonary arteries.

  1998cited by this paper
• Attenuated K+ channel gene transcription in primary pulmonary hypertension.

  1998cited by this paper
• ATP-sensitive and inwardly rectifying potassium channels in smooth muscle.

  1997influential reference
• Modulation of inwardly rectifying potassium channels in cultured bovine pulmonary artery endothelial cells

  1997cited by this paper
• Evaluation of bosentan, pinacidil and nitroprusside on human pulmonary arteries: comparison with rat pulmonary arteries *

  1997cited by this paper
• Physiological roles and properties of potassium channels in arterial smooth muscle.

  1995influential reference
• Chronic hypoxia is associated with reduced delayed rectifier K+ current in rat pulmonary artery muscle cells.

  1994cited by this paper
• Calcitonin gene‐related peptide activated ATP‐sensitive K+ currents in rabbit arterial smooth muscle via protein kinase A.

  1994influential reference
• Inward rectifier K+ currents in smooth muscle cells from rat resistance-sized cerebral arteries.

  1993cited by this paper
• ATP-sensitive K+ channels regulate resting potential of pulmonary arterial smooth muscle cells.

  1992cited by this paper
• Opposing actions of tolbutamide and glibenclamide on hypoxic pulmonary vasoconstriction.

  1992cited by this paper
• Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone.

  1990cited by this paper
• Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle.

  1989cited by this paper
• Flow control among microvessels coordinated by intercellular conduction.

  1986cited by this paper
• Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats.

  1977influential reference

• No citing papers are available for this paper.