Potassium channels in pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder with various origins. All forms of PAH share a common pulmonary arteriopathy characterised by vasoconstriction, remodelling of the pre-capillary pulmonary vessel wall, and in situ thrombosis. Although the pathogenesis of PAH is recognised as a complex and multifactorial process, there is growing evidence that potassium channels dysfunction in pulmonary artery smooth muscle cells is a hallmark of PAH. Besides regulating many physiological functions, reduced potassium channels expression and/or activity have significant effects on PAH establishment and progression. This review describes the molecular mechanisms and physiological consequences of potassium channel modulation. Special emphasis is placed on KCNA5 (Kv1.5) and KCNK3 (TASK1), which are considered to play a central role in determining pulmonary vascular tone and may represent attractive therapeutic targets in the treatment of PAH.
Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada olivier.boucherat@criucpq.ulaval.ca.
Olivier
O
Boucherat
Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada.
Sophie
S
Chabot
Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada UMRS 999, INSERM and Univ. Paris-Sud, Laboratoire d'Excellence (LabEx) en Recherche sur le Médicament et l'Innovation Thérapeutique (LERMIT), Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
Fabrice
F
Antigny
Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada UMRS 999, INSERM and Univ. Paris-Sud, Laboratoire d'Excellence (LabEx) en Recherche sur le Médicament et l'Innovation Thérapeutique (LERMIT), Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
Frédéric
F
Perros
Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada.
Steeve
S
Provencher
Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada.
Sébastien
S
Bonnet
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D016923:Cell Death; D049109:Cell Proliferation; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D051666:Kv1.5 Potassium Channel / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015221:Potassium Channels / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011651:Pulmonary Artery / Q000473:pathology; D015398:Signal Transduction; D013927:Thrombosis / Q000503:physiopathology; D014661:Vasoconstriction
D019485:Bone Morphogenetic Proteins; C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3