Pathogenic Roles of Ca2+ and Ion Channels in Hypoxia-Mediated Pulmonary Hypertension

Chronic hypoxia causes pulmonary hypertension (CHPH), which occurs in residents living in high altitude and patients with chronic obstructive pulmonary disease, interstitial lung disease, and sleep-disordered breathing. The pathogenic mechanisms of CHPH are unclear, but involve sustained vasoconstriction and excessive vascular remodeling. A rise in cytosolic Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells is a major trigger for pulmonary vasoconstriction and an important stimulus for vascular smooth muscle proliferation. Multiple ion channels in the plasma membrane participate in the regulation of [Ca2+]cyt, while hypoxia upregulates Ca2+ channels and downregulates K+ channels in pulmonary vascular smooth muscle cells. This chapter discusses the potential mechanism by which hypoxia causes pulmonary hypertension via modulating Ca2+ and K+ channel expression and function, and regulating intracellular Ca2+ stores in the sarcoplasmic reticulum.