{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:48:29Z","timestamp":1772999309128,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"\n Abstract<\/jats:title>\n \n The resting membrane potential (V\n M<\/jats:sub>\n ) 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\n +<\/jats:sup>\n channels responsible for setting the V\n M<\/jats:sub>\n of smooth muscle cells (SMCs) and endothelial cells (ECs) remain incompletely defined. This study investigated whether inwardly rectifying (Kir2) and ATP\u2010sensitive (K\n ATP<\/jats:sub>\n ) K\n +<\/jats:sup>\n channels are functionally expressed in native human pulmonary artery (PA) SMCs and ECs and assessed their contribution to vascular tone. Combining patch\u2010clamp 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\n 2+<\/jats:sup>\n \u2010sensitive inward currents with a characteristic rectification profile, supported by immunolabelling of Kir2.1 and Kir2.2 subunits. Functionally, BaCl\n 2<\/jats:sub>\n induced concentration\u2010dependent contractions of PA rings and significantly attenuated acetylcholine\u2010evoked, endothelium\u2010dependent relaxation, revealing a tonic vasodilatory role for Kir2 channels. K\n ATP<\/jats:sub>\n currents, activated by pinacidil and blocked by glibenclamide and PNU\u201037883A, were also observed in PASMCs and PAECs, consistent with immunodetection of Kir6.1 and SUR2 subunits. In isolated PAs, pinacidil elicited concentration\u2010dependent vasodilatation, which was significantly reduced by K\n ATP<\/jats:sub>\n channel blockade. Collectively, these findings demonstrate for the first time the functional presence of Kir2 and K\n ATP<\/jats:sub>\n channels in native human pulmonary vascular cells, and their modulatory role on V\n M<\/jats:sub>\n and arterial tone. These channels emerge as key electro\u2010metabolic regulators of pulmonary vascular function and promising therapeutic targets in diseases characterized by V\n M<\/jats:sub>\n dysregulation, such as pulmonary arterial hypertension.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n Inwardly rectifying (Kir2) K\n +<\/jats:sup>\n channels are key regulators of the resting membrane potential (V\n M<\/jats:sub>\n ) in different vascular cell types across multiple vascular beds, whereas ATP\u2010sensitive (K\n ATP<\/jats:sub>\n ) K\n +<\/jats:sup>\n channels detect changes in the metabolic state of vascular cells and translate these changes into V\n M<\/jats:sub>\n modulation.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Despite their well\u2010established physiological relevance, a comprehensive characterization of Kir2 and K\n ATP<\/jats:sub>\n channels in freshly isolated human pulmonary vascular cells \u2013 particularly within the endothelium \u2013 remains lacking.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Our study provides compelling evidence for the functional expression of Kir2 and K\n ATP<\/jats:sub>\n channels in native human pulmonary arterial smooth muscle and endothelial cells, demonstrating their contribution to V\n M<\/jats:sub>\n regulation and pulmonary vascular tone at rest and in response to specific stimuli.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp289445","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T09:07:24Z","timestamp":1769591244000},"page":"1820-1839","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional expression of inwardly rectifying and ATP\u2010sensitive potassium channels in human pulmonary artery smooth muscle and endothelial cells"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0338-8456","authenticated-orcid":false,"given":"Bianca","family":"Barreira","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology School of Medicine Universidad Complutense de Madrid Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES) Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) Madrid Spain"}]},{"given":"Daniel","family":"Morales\u2010Cano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology School of Medicine Universidad Complutense de Madrid Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES) Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) Madrid Spain"}]},{"given":"Laura","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology School of Medicine Universidad Complutense de Madrid Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES) Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) Madrid Spain"}]},{"given":"Beatriz","family":"de Olaiz","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Hospital Universitario de Getafe Getafe Spain"}]},{"given":"Rui","family":"Ad\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology School of Medicine Universidad Complutense de Madrid Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES) Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) Madrid Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1382-1698","authenticated-orcid":false,"given":"Angel","family":"Cogolludo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology School of Medicine Universidad Complutense de Madrid Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES) Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) Madrid Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6309-7418","authenticated-orcid":false,"given":"Francisco","family":"Perez\u2010Vizcaino","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology School of Medicine Universidad Complutense de Madrid Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES) Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) Madrid Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4750-1040","authenticated-orcid":false,"given":"Maria","family":"Sancho","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES) Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) Madrid Spain"},{"name":"Department of Physiology School of Medicine Universidad Complutense de Madrid Madrid Spain"},{"name":"Department of Pharmacology University of Vermont Burlington Vermont USA"}]}],"member":"311","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273255"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020951"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00511.2002"},{"issue":"3","key":"e_1_2_5_5_1","first-page":"H916","article-title":"ATP\u2010sensitive K+ channels regulate resting potential of pulmonary arterial smooth muscle cells","volume":"262","author":"Clapp L. H.","year":"1992","journal-title":"American Journal of Physiology"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn349"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.26.1.4622"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.3.H887"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/2045-8932.78103"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.114.3_Supplement.208S"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2011.tb00306.x"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2018.160"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/10739680590896072"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.545bd.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.1066047"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000365"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4533"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000175877.25296.bd"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2011.tb00358.x"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00353.x"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00035.2022"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107835"},{"issue":"6","key":"e_1_2_5_23_1","first-page":"00350","article-title":"Pulmonary hypertension associated with diazoxide: The SUR1 paradox","volume":"9","author":"Montani D.","year":"2023","journal-title":"European Respiratory Journal Open Research"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.41.1.19"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1990.259.1.C3"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.268.4.C799"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00044.2018"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000261658.12024.18"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP279570"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1998.275.6.L1069"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2015-208067"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36563"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.5.C1540"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020045"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.265.5.C1363"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.4.1165"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0742-8413(92)90143-U"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP284936"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312493"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2024.03.004"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abl5405"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3775368"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00469.2001"},{"issue":"1","key":"e_1_2_5_44_1","first-page":"H365","article-title":"Chronic hypoxia is associated with reduced delayed rectifier K+ current in rat pulmonary artery muscle cells","volume":"266","author":"Smirnov S. V.","year":"1994","journal-title":"The American Journal of Physiology"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1216283"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271652"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2501869"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00041.2010"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-006-0037-y"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2017.tb00747.x"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.1997.tb00864.x"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010617-052623"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.14.1400"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)78495-6"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922095117"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP289445","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP289445","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP289445","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:09:34Z","timestamp":1772989774000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP289445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":54,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1113\/JP289445"],"URL":"https:\/\/doi.org\/10.1113\/jp289445","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]},"assertion":[{"value":"2025-06-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}