{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:22:11Z","timestamp":1785424931292,"version":"3.56.0"},"reference-count":76,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R15 HL141963"],"award-info":[{"award-number":["R15 HL141963"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01 HL169297"],"award-info":[{"award-number":["R01 HL169297"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R15 HL141963"],"award-info":[{"award-number":["R15 HL141963"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 HL169297"],"award-info":[{"award-number":["R01 HL169297"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"crossref","award":["5I01BX004954"],"award-info":[{"award-number":["5I01BX004954"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"award":["5I01BX004954"],"award-info":[{"award-number":["5I01BX004954"]}],"id":[{"id":"https:\/\/ror.org\/05dbx6743","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["18AIREA 33960175"],"award-info":[{"award-number":["18AIREA 33960175"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["23IPA1046060"],"award-info":[{"award-number":["23IPA1046060"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"award":["18AIREA 33960175"],"award-info":[{"award-number":["18AIREA 33960175"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]},{"award":["23IPA1046060"],"award-info":[{"award-number":["23IPA1046060"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Robert J. Kleberg, Jr., and Helen C. Kleberg Foundation"},{"id":[{"id":"https:\/\/ror.org\/05r5zfp34","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007144","name":"University of Houston","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007144","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/048sx0r50","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Two-pore domain potassium (K2P) channels are the most recently identified family of potassium channels. They are regarded as the largest group of background \u201cleak\u201d channels, encoded by 15 mammalian KCNK genes, and divided into six subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). These channels have a role in stabilizing the resting membrane potential. Their widespread presence in the heart and vasculature supports cellular homeostasis by regulating cardiac rhythm, vascular tone, and protection against ischemic stress. The TASK, TWIK, and TREK subfamilies are the most abundantly expressed K2P channel subfamilies in the cardiovascular system, and dysregulation of specific members has been strongly linked to the development of major cardiovascular diseases. Mutations in TASK-1 have been identified in patients with pulmonary arterial hypertension, providing human genetic evidence linking K2P dysfunction to pulmonary vascular disease. While alterations in other K2P channels, such as TREK-1, have been demonstrated in preclinical studies where reduced channel activity is associated with ischemia\u2013reperfusion injury and promotes cardiac arrhythmias. Growing evidence suggests that K2P channels could serve as promising therapeutic targets, with pharmacological activation of TASK-1 and TREK-1, for instance, that might help restore vascular tone, reduce remodeling, and offer cardioprotection. Their unique leak-channel properties enable the development of highly selective treatments. This review addresses the molecular biology, physiological roles, and disease relevance of K2P channels in the cardiovascular and pulmonary systems, emphasizing their potential as targets for innovative therapies in cardiovascular diseases.<\/jats:p>","DOI":"10.3390\/ph19040533","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:05:33Z","timestamp":1774451133000},"page":"533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["K2P Channels as Key Regulators of Cardiovascular and Pulmonary Vascular Function"],"prefix":"10.3390","volume":"19","author":[{"given":"Hala Y.","family":"Abdelnasser","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204-5037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinchun","family":"Pi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5071-5184","authenticated-orcid":false,"given":"Lavannya M.","family":"Pandit","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8712-0336","authenticated-orcid":false,"given":"Bradley K.","family":"McConnell","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204-5037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1152\/physrev.00029.2009","article-title":"Molecular Background of Leak K Currents: Two-Pore Domain Potassium Channels","volume":"90","author":"Enyedi","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Herrera-P\u00e9rez, S., Campos-R\u00edos, A., Rueda-ruzafa, L., and Lamas, J.A. (2021). Contribution of K2P Potassium Channels to Cardiac Physiology and Pathophysiology. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126635"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"F793","DOI":"10.1152\/ajprenal.2000.279.5.F793","article-title":"Molecular and Functional Properties of Two-Pore-Domain Potassium Channels","volume":"279","author":"Lesage","year":"2000","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1113\/jphysiol.2014.287268","article-title":"The Family of K2P Channels: Salient Structural and Functional Properties","volume":"593","author":"Feliciangeli","year":"2015","journal-title":"J. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5464","DOI":"10.1093\/emboj\/16.17.5464","article-title":"TASK, a Human Background K Channel to Sense External PH Variations near Physiological PH","volume":"16","author":"Duprat","year":"1997","journal-title":"EMBO J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1002\/j.1460-2075.1996.tb00437.x","article-title":"TWIK-1, a Ubiquitous Human Weakly Inward Rectifying K+ Channel with a Novel Structure","volume":"15","author":"Lesage","year":"1996","journal-title":"EMBO J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s12013-007-0007-8","article-title":"Biophysical, Pharmacological, and Functional Characteristics of Cloned and Native Mammalian Two-Pore Domain K+ Channels","volume":"47","author":"Lotshaw","year":"2007","journal-title":"Cell Biochem. Biophys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28722","DOI":"10.1074\/jbc.M003755200","article-title":"TWIK-2, an Inactivating 2P Domain K+ Channel","volume":"275","author":"Patel","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wiedmann, F., Frey, N., and Schmidt, C. (2021). Two-Pore-Domain Potassium (K2p-) Channels: Cardiac Expression Patterns and Disease-Specific Remodelling Processes. Cells, 10.","DOI":"10.3390\/cells10112914"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1161\/HYPERTENSIONAHA.111.179390","article-title":"Two-Pore Domain K+ Channels: Evidence for TWIK-2 in Blood Pressure Regulation","volume":"58","author":"Pathan","year":"2011","journal-title":"Hypertension"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1161\/HYPERTENSIONAHA.114.03406","article-title":"TWIK-2 Channel Deficiency Leads to Pulmonary Hypertension Through a Rho-Kinase-Mediated Process","volume":"64","author":"Pandit","year":"2014","journal-title":"Hypertension"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Djillani, A., Mazella, J., Heurteaux, C., and Borsotto, M. (2019). Role of TREK-1 in Health and Disease, Focus on the Central Nervous System. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00379"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5182","DOI":"10.1111\/bph.12596","article-title":"Modulation of K2P2.1 and K2P10.1 K+ Channel Sensitivity to Carvedilol by Alternative MRNA Translation Initiation","volume":"171","author":"Kisselbach","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"27406","DOI":"10.1074\/jbc.M206810200","article-title":"A Novel Two-Pore Domain K+ Channel, TRESK, Is Localized in the Spinal Cord","volume":"278","author":"Sano","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"14677","DOI":"10.1074\/jbc.M602495200","article-title":"Targeting of Calcineurin to an NFAT-like Docking Site Is Required for the Calcium-Dependent Activation of the Background K+ Channel, TRESK","volume":"281","author":"Enyedi","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26499","DOI":"10.1074\/jbc.M010357200","article-title":"Combined Antisense and Pharmacological Approaches Implicate HTASK as an Airway O2 Sensing K+Channel","volume":"276","author":"Hartness","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1124\/mi.3.4.205","article-title":"The TASK Family: Two-Pore Domain Background K+ Channels","volume":"3","author":"Bayliss","year":"2003","journal-title":"Mol. Interv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1006\/bbrc.2001.4562","article-title":"Genomic and Functional Characteristics of Novel Human Pancreatic 2P Domain K+ Channels","volume":"282","author":"Girard","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6854","DOI":"10.1002\/j.1460-2075.1996.tb01077.x","article-title":"Cloning, Functional Expression and Brain Localization of a Novel Unconventional Outward Rectifier K+ Channel","volume":"15","author":"Fink","year":"1996","journal-title":"EMBO J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1213\/01.ane.0000168447.87557.5a","article-title":"Species-Spicific Differences in Response to Anes-Thetics and Other Modulators by the K2P Channel TRESK","volume":"101","author":"Keshavaprasad","year":"2005","journal-title":"Anesth. Analg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"107835","DOI":"10.1016\/j.pharmthera.2021.107835","article-title":"Potassium (K+) Channels in the Pulmonary Vasculature: Implications in Pulmonary Hypertension Physiological, Pathophysiological and Pharmacological Regulation","volume":"225","author":"Cogolludo","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s00424-018-2151-y","article-title":"Calcium- and Voltage-Gated BK Channels in Vascular Smooth Muscle","volume":"470","author":"Dopico","year":"2018","journal-title":"Pfl\u00fcgers Arch.-Eur. J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.drudis.2012.04.002","article-title":"Function and Regulation of Large Conductance Ca2+-Activated K+ Channel in Vascular Smooth Muscle Cells","volume":"17","author":"Hu","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s00424-008-0491-8","article-title":"The Non-Excitable Smooth Muscle: Calcium Signaling and Phenotypic Switching during Vascular Disease","volume":"456","author":"House","year":"2008","journal-title":"Pfl\u00fcgers Arch.-Eur. J. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.pbiomolbio.2020.05.007","article-title":"Mechanosensitive TREK-1 Two-Pore-Domain Potassium (K2P) Channels in the Cardiovascular System","volume":"159","author":"Wiedmann","year":"2021","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00249-008-0326-8","article-title":"Two-Pore Potassium Channels in the Cardiovascular System","volume":"38","author":"Gurney","year":"2009","journal-title":"Eur. Biophys. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1177\/1074248417729880","article-title":"Cardiac Potassium Channels: Physiological Insights for Targeted Therapy","volume":"23","author":"Jeevaratnam","year":"2018","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1038\/bjp.2008.213","article-title":"Regulation of Two-Pore-Domain (K 2P) Potassium Leak Channels by the Tyrosine Kinase Inhibitor Genistein","volume":"154","author":"Gierten","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1161\/CIRCULATIONAHA.114.012657","article-title":"Upregulation of K2P3.1 K+ Current Causes Action Potential Shortening in Patients with Chronic Atrial Fibrillation","volume":"132","author":"Schmidt","year":"2015","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00395-018-0687-9","article-title":"Atrial Fibrillation and Heart Failure-Associated Remodeling of Two-Pore-Domain Potassium (K2P) Channels in Murine Disease Models: Focus on TASK-1","volume":"113","author":"Wiedmann","year":"2018","journal-title":"Basic Res. Cardiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sagris, M., Vardas, E.P., Theofilis, P., Antonopoulos, A.S., Oikonomou, E., and Tousoulis, D. (2022). Atrial Fibrillation: Pathogenesis, Predisposing Factors, and Genetics. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010006"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/j.1440-1681.2004.03964.x","article-title":"Heterogeneous Expression of Tandem-Pore K+ Channel Genes in Adult and Embryonic Rat Heart Quantified by Real-Time Polymerase Chain Reaction","volume":"31","author":"Liu","year":"2004","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Le Ribeuz, H., Montani, D., and Antigny, F. (2021). The Experimental TASK-1 Potassium Channel Inhibitor A293 Can Be Employed for Rhythm Control of Persistent Atrial Fibrillation in a Translational Large Animal Model. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.668267"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mond\u00e9jar-Parre\u00f1o, G. (2022). Unraveling the Role of K2P Channels in Atrial Fibrillation. Front. Biosci.-Sch., 14.","DOI":"10.31083\/j.fbs1404031"},{"key":"ref_35","first-page":"376","article-title":"Atrial Fibrillation in Patients with Systolic Heart Failure: Pathophysiology Mechanisms and Management","volume":"18","author":"Koniari","year":"2021","journal-title":"J. Geriatr. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.1007\/s00210-023-02569-4","article-title":"Exploring the Involvement of TASK-1 in the Control of Isolated Rat Right Atrium Function from Healthy Animals and an Experimental Model of Monocrotaline-Induced Pulmonary Hypertension","volume":"396","year":"2023","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMoa1211097","article-title":"A Novel Channelopathy in Pulmonary Arterial Hypertension","volume":"369","author":"Ma","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1161\/HYPERTENSIONAHA.116.07564","article-title":"KCNK3 Variants Are Associated with Hyperaldosteronism and Hypertension","volume":"68","author":"Manichaikul","year":"2016","journal-title":"Hypertension"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.yjmcc.2015.01.017","article-title":"TASK-1 and TASK-3 May Form Heterodimers in Human Atrial Cardiomyocytes","volume":"81","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"937","DOI":"10.15252\/emmm.201303783","article-title":"Gain-of-function Mutation in TASK-4 Channels and Severe Cardiac Conduction Disorder","volume":"6","author":"Friedrich","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/j.jtcvs.2004.08.031","article-title":"Comparing the Global MRNA Expression Profile of Human Atrial and Ventricular Myocardium with High-Density Oligonucleotide Arrays","volume":"129","author":"Ellinghaus","year":"2005","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1161\/HYPERTENSIONAHA.111.175349","article-title":"Disruption of K2P6.1 Produces Vascular Dysfunction and Hypertension in Mice","volume":"58","author":"Lloyd","year":"2011","journal-title":"Hypertension"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1007\/s00424-019-02306-y","article-title":"TREK-1 Protects the Heart against Ischemia-Reperfusion-Induced Injury and from Adverse Remodeling after Myocardial Infarction","volume":"471","author":"Kamatham","year":"2019","journal-title":"Pflugers Arch."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s00395-016-0597-7","article-title":"TREK-1 (K2P2.1) K+ Channels Are Suppressed in Patients with Atrial Fibrillation and Heart Failure and Provide Therapeutic Targets for Rhythm Control","volume":"112","author":"Lugenbiel","year":"2017","journal-title":"Basic Res. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1111\/bph.16426","article-title":"The TREK-1 Potassium Channel Is a Potential Pharmacological Target for Vasorelaxation in Pulmonary Hypertension","volume":"181","year":"2024","journal-title":"Br. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1152\/ajplung.00078.2011","article-title":"Regulation and Function of the Two-Pore-Domain (K2P) Potassium Channel Trek-1 in Alveolar Epithelial Cells","volume":"302","author":"Schwingshackl","year":"2012","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.pbiomolbio.2017.05.004","article-title":"Stretch-Activated Two-Pore-Domain (K2P) Potassium Channels in the Heart: Focus on Atrial Fibrillation and Heart Failure","volume":"130","author":"Schmidt","year":"2017","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1152\/ajpheart.00739.2018","article-title":"TASK-1 and TASK-3 Channels Modulate Pressure over-Load-Induced Cardiac Remodeling and Dysfunction","volume":"318","author":"Duan","year":"2020","journal-title":"Am. J. Physiol. Hear. Circ. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1161\/CIRCULATIONAHA.104.506857","article-title":"Human Atrial Ion Channel and Transporter Subunit Gene-Expression Remodeling Associated with Valvular Heart Disease and Atrial Fibrillation","volume":"112","author":"Gaborit","year":"2005","journal-title":"Circulation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4843","DOI":"10.1172\/JCI95945","article-title":"The Two-Pore Domain Potassium Channel TREK-1 Mediates Cardiac Fibrosis and Diastolic Dysfunction","volume":"128","author":"Abraham","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00210-009-0487-8","article-title":"Novel Pharmacological Approaches for Antiarrhythmic Therapy","volume":"381","author":"Ravens","year":"2010","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Shvetsova, A.A., Lazarenko, V.S., Gaynullina, D.K., Tarasova, O.S., and Schubert, R. (2022). TWIK-Related Acid-Sensitive Potassium Channels (TASK-1) Emerge as Contributors to Tone Regulation in Renal Arteries at Alkaline PH. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.895863"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1700754","DOI":"10.1183\/13993003.00754-2017","article-title":"TASK-1 (KCNK3) Channels in the Lung: From Cell Biology to Clinical Implications","volume":"50","author":"Olschewski","year":"2017","journal-title":"Eur. Respir. Soc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3103\/S0096392522020109","article-title":"TASK-1 Channels: Functional Role in Arterial Smooth Muscle Cells","volume":"77","author":"Shvetsova","year":"2022","journal-title":"Mosc. Univ. Biol. Sci. Bull."},{"key":"ref_55","first-page":"530","article-title":"Regulation of Monocyte Chemotactic Protein-1 Secretion by the Two-Pore-Domain Potassium (K2P) Channel TREK-1 in Human Alveolar Epithelial Cells","volume":"5","author":"Schwingshackl","year":"2013","journal-title":"Am. J. Transl. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"22011","DOI":"10.1038\/s41598-020-78886-y","article-title":"K2P2.1 (TREK-1) Potassium Channel Activation Protects against Hyperoxia-Induced Lung Injury","volume":"10","author":"Zyrianova","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s13054-019-2539-x","article-title":"Influenza Virus-Related Critical Illness: Pathophysiology and Epidemiology","volume":"23","author":"Kalil","year":"2019","journal-title":"Crit. Care"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"L64","DOI":"10.1152\/ajplung.00116.2022","article-title":"Activation of TREK-1 (K2P2.1) Potassium Channels Protects against Influenza A-Induced Lung Injury","volume":"324","author":"Zyrianova","year":"2023","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"L367","DOI":"10.1152\/ajplung.00313.2023","article-title":"Two-Pore Potassium Channel TREK-1 (K2P2.1) Regulates NLRP3 Inflammasome Activity in Macrophages","volume":"326","author":"Immanuel","year":"2024","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1186\/s12931-020-01570-2","article-title":"Pulmonary Hypertension Secondary to Pulmonary Fibrosis: Clinical Data, Histopathology and Molecular Insights","volume":"21","author":"Ruffenach","year":"2020","journal-title":"Respir. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.jacc.2004.02.037","article-title":"Clinical Classification of Pulmonary Hypertension","volume":"43","author":"Simonneau","year":"2004","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"216","DOI":"10.7326\/0003-4819-107-2-216","article-title":"Primary Pulmonary Hypertension: A National Prospective Study","volume":"107","author":"Rich","year":"1987","journal-title":"Ann. Intern. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","article-title":"2022 ESC\/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension","volume":"43","author":"Humbert","year":"2022","journal-title":"Eur. Hear. J."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Shima, N. (2024). Up-Regulated Expression of Two-Pore Domain K+ Channels, KCNK1 and KCNK2, Is Involved in the Proliferation and Migration of Pulmonary Arterial Smooth Muscle Cells in Pulmonary Arterial Hypertension. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1343804"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.recesp.2016.05.029","article-title":"Molecular Genetic Diagnosis of Pulmonary Arterial Hypertension: An Increased Complexity","volume":"69","author":"Eyries","year":"2016","journal-title":"Rev. Esp. Cardiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1113\/JP277275","article-title":"Characterization and Regulation of Wild-Type and Mutant TASK-1 Two Pore Domain Potassium Channels Indicated in Pulmonary Arterial Hypertension","volume":"597","author":"Cunningham","year":"2019","journal-title":"J. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Bohnen, M.S. (2017). The Impact of Heterozygous KCNK3 Mutations Associated with Pulmonary Arterial Hypertension on Channel Function and Pharmacological Recovery. J. Am. Hear. Assoc., 6.","DOI":"10.1161\/JAHA.117.006465"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1161\/CIRCULATIONAHA.115.020951","article-title":"Potassium Channel Subfamily K Member 3 (KCNK3) Contributes to the Development of Pulmonary Arterial Hypertension","volume":"133","author":"Antigny","year":"2016","journal-title":"Circulation"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1053\/pcad.2002.130041","article-title":"Molecular and Cellular Basis of Pulmonary Vascular Remodeling in Pulmonary Hypertension","volume":"45","author":"Jeffery","year":"2002","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kanai, S.M., and Clouthier, D.E. (2023). Endothelin Signaling in Development. Development, 150.","DOI":"10.1242\/dev.201786"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1124\/pr.115.011833","article-title":"Endothelin","volume":"68","author":"Davenport","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jash.2008.09.002","article-title":"Vascular Smooth Muscle Cell Signaling Mechanisms for Contraction to Angiotensin II and Endothelin-1","volume":"3","author":"Wynne","year":"2009","journal-title":"J. Am. Soc. Hypertens."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1165\/rcmb.2008-0412OC","article-title":"Endothelin-1 Inhibits Background Two-Pore Domain Channel TASK-1 in Primary Human Pulmonary Artery Smooth Muscle Cells","volume":"41","author":"Tang","year":"2009","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1113\/jphysiol.2006.121582","article-title":"Neuronal Two-Pore-Domain Potassium Channels and Their Regulation by G Protein-Coupled Receptors","volume":"578","author":"Mathie","year":"2007","journal-title":"J. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e76","DOI":"10.1161\/CIRCRESAHA.124.324455","article-title":"Genome-Wide Methylation Analysis Reveals a KCNK3-Prominent Causal Cascade on Hypertension","volume":"135","author":"Huang","year":"2024","journal-title":"Circ. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1111\/j.1476-5381.2011.01319.x","article-title":"Carvedilol Targets Human K2P3.1 (TASK1) K+ Leak Channels","volume":"163","author":"Staudacher","year":"2011","journal-title":"Br. J. 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