Effects of Mitochondrial Potassium Channel and Membrane Potential on Hypoxic Human Pulmonary Artery Smooth Muscle Cells

Chronic hypoxia induces proliferation of human pulmonary artery smooth muscle cells (hPASMCs), leading to remodeling and pulmonary hypertension, but the mechanism remains unclear. The present study tested the roles of mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) and mitochondrial membrane potential (Delta Psi(m)) on hPASMCs under normoxic or hypoxic conditions. Our results demonstrated that diazoxide or hypoxia, alone or in combination, could depolarize Delta Psi(m) through opening mitoK(ATP), release of cytochrome C, and overproduction of hydrogen peroxide by mitochondria, resulting in increased proliferation and decreased apoptosis of hPASMCs. Five-hydroxydecanoate could partly reduce these hypoxia-dependent responses. These results suggest that the opening of mitoK(ATP) followed by a depolarization of Delta Psi(m) might play an important role in hypoxic proliferation of hPASMCs through cytochrome C accumulation within the mitochondria or mitochondrial overproduction of hydrogen peroxide.