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

Potassium 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.