Effects of mitochondrial potassium channel and membrane potential on hypoxic human pulmonary artery smooth muscle cells

• Published in: American journal of respiratory cell and molecular biology Vol. 42; no. 6; pp. 661 - 666
• Main Authors: Hu, Hong-Ling, Zhang, Zhen-Xiang, Chen, Cheng-Shui, Cai, Chang, Zhao, Jian-Ping, Wang, Xiangdong
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.06.2010
• Subjects: Apoptosis; Cell Hypoxia; Cell Proliferation; Cells, Cultured; Cytochromes c - metabolism; Decanoic Acids - pharmacology; Diazoxide - pharmacology; Humans; Hydrogen Peroxide - metabolism; Hydroxy Acids - pharmacology; Membrane Potential, Mitochondrial - drug effects; Mitochondria, Muscle - drug effects; Mitochondria, Muscle - metabolism; Mitochondria, Muscle - pathology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Potassium Channels - metabolism; Pulmonary Artery - metabolism
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2009-0017oc

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 (DeltaPsi(m)) on hPASMCs under normoxic or hypoxic conditions. Our results demonstrated that diazoxide or hypoxia, alone or in combination, could depolarize DeltaPsi(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 DeltaPsi(m) might play an important role in hypoxic proliferation of hPASMCs through cytochrome C accumulation within the mitochondria or mitochondrial overproduction of hydrogen peroxide.