Smooth muscle cell ion channels in pulmonary arterial hypertension: Pathogenic role in pulmonary vasoconstriction and vascular remodeling

Pulmonary arterial hypertension (PAH) is a progressive hemodynamic disease that impacts right heart function ultimately resulting in mortality due to right heart failure. Increased pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP) observed in PAH patients can be attributed in part to sustained vasoconstriction and excessive remodeling of the distal pulmonary arteries. Pulmonary vasoconstriction is a result of pulmonary artery smooth muscle cell (PASMC) contraction while pulmonary vascular remodeling is associated with increased cell proliferation and decreased apoptosis. Spanning the plasma membrane of PASMC are macromolecular pore-forming proteins known as ion channels that allow for passive distribution of ion across the membrane when open. Ion channel activity is crucial for driving critical physiological functions. Posttranscriptional regulation of ion channel expression and ion channel dysfunction in PASMCs have been linked to changes in vascular tone and the initiation of vascular remodeling. This chapter will introduce smooth muscle cell ion channels that regulate physiological function in the pulmonary vasculature and summarize their potential pathogenic contribution to the development of pulmonary vascular diseases such as PAH.