Ca2+ and ion channels in hypoxia-mediated pulmonary hypertension

Alveolar hypoxia, a consequence of many lung diseases, can have adverse effects on the pulmonary vasculature. The changes that occur in the pulmonary circulation with exposure to chronic hypoxia include reductions in the diameter of the pulmonary arteries due to structural remodeling of the vasculature. Although the structural and functional changes that occur in the development of pulmonary hypertension have been well investigated, less is known about the cellular and molecular mechanisms of this process. This review will discuss the role of several potassium and calcium channels in hypoxic pulmonary vasoconstriction, both in elevating calcium influx into pulmonary artery smooth muscle cells (PASMCs). In addition to other signal transduction pathways, Ca²⁺ signaling in PASMCs plays an important role in the development and progression of pulmonary hypertension due to its central roles in vasoconstriction and vascular remodeling. This review will focus on the effect of chronic hypoxia on ion channels and the potential pathogenic role of Ca²⁺ signaling and regulation in the progression of pulmonary hypertension.