Physiological and pathophysiological roles of the KCNK3 potassium channel in the pulmonary circulation and the heart

Author:

Saint‐Martin Willer Anaïs12ORCID,Santos‐Gomes Joana3,Adão Rui3456ORCID,Brás‐Silva Carmen3,Eyries Mélanie78,Pérez‐Vizcaino Francisco456ORCID,Capuano Véronique12,Montani David129,Antigny Fabrice12ORCID

Affiliation:

1. Université Paris‐Saclay Faculté de Médecine Le Kremlin‐Bicêtre France

2. INSERM UMR_S 999 ‘Hypertension Pulmonaire: Physiopathologie et Innovation Thérapeutique’ Hôpital Marie Lannelongue Le Plessis‐Robinson France

3. Cardiovascular R&D Centre‐UnIC@RISE, Department of Surgery and Physiology Faculty of Medicine of the University of Porto Porto Portugal

4. Department of Pharmacology and Toxicology, School of Medicine Universidad Complutense de Madrid Madrid Spain

5. Instituto de Investigación Sanitaria Gregorio Marañón (IISGM) Madrid Spain

6. CIBER Enfermedades Respiratorias (Ciberes) Madrid Spain

7. Département de génétique Assistance Publique‐Hôpitaux de Paris, Hôpital Pitié‐Salpêtrière Sorbonne Université Paris France

8. INSERM UMRS1166, ICAN – Institute of CardioMetabolism and Nutrition Sorbonne Université Paris France

9. Assistance Publique – Hôpitaux de Paris (AP‐HP), Service de Pneumologie et Soins Intensifs Respiratoires Centre de Référence de l'Hypertension Pulmonaire, Hôpital Bicêtre Le Kremlin‐Bicêtre France

Abstract

AbstractPotassium channel subfamily K member 3 (KCNK3), encoded by the KCNK3 gene, is part of the two‐pore domain potassium channel family, constitutively active at resting membrane potentials in excitable cells, including smooth muscle and cardiac cells. Several physiological and pharmacological mediators, such as intracellular signalling pathways, extracellular pH, hypoxia and anaesthetics, regulate KCNK3 channel function. Recent studies show that modulation of KCNK3 channel expression and function strongly influences pulmonary vascular cell and cardiomyocyte function. The altered activity of KCNK3 in pathological situations such as atrial fibrillation, pulmonary arterial hypertension and right ventricular dysfunction demonstrates the crucial role of KCNK3 in cardiovascular homeostasis. Furthermore, loss of function variants of KCNK3 have been identified in patients suffering from pulmonary arterial hypertension and atrial fibrillation. This review focuses on current knowledge of the role of the KCNK3 channel in pulmonary circulation and the heart, in healthy and pathological conditions. image

Funder

Agence Nationale de la Recherche

Publisher

Wiley

Subject

Physiology

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