Augmented K+ currents and mitochondrial membrane depolarization in pulmonary artery myocyte apoptosis

The balance between apoptosis and proliferation in pulmonary artery smooth muscle cells (PASMCs) is important in maintaining normal pulmonary vascular structure. Activity of voltage-gated K+ (KV) channels has been demonstrated to regulate cell apoptosis and proliferation. Treatment of PASMCs with staurosporine (ST) induced apoptosis in PASMCs, augmented KV current [I K(V)], and induced mitochondrial membrane depolarization. High K+ (40 mM) negligibly affected the ST-induced mitochondrial membrane depolarization but inhibited the ST-induced I K(V) increase and apoptosis. Blockade of KV channels with 4-aminopyridine diminishedI K(V) and markedly decreased the ST-mediated apoptosis. Furthermore, the ST-induced apoptosis was preceded by the increase in I K(V). These results indicate that ST induces PASMC apoptosis by activation of plasmalemmal KV channels and mitochondrial membrane depolarization. The increased I K(V) would result in an apoptotic volume decrease due to a loss of cytosolic K+ and induce apopto...