| 11557592 |
Krick S, Platoshyn O, McDaniel SS, Rubin LJ, Yuan JX: Augmented K (+) currents and mitochondrial membrane depolarization in pulmonary artery myocyte apoptosis. Am J Physiol Lung Cell Mol Physiol. 2001 Oct;281(4):L887-94.
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 (+) (K (V)) channels has been demonstrated to regulate cell apoptosis and proliferation. Treatment of PASMCs with staurosporine (ST) induced apoptosis in PASMCs, augmented K (V) 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 K (V) channels with 4-aminopyridine diminished I (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 K (V) 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 apoptosis. The mitochondrial membrane depolarization would cause cytochrome c release, activate the cytosolic caspases, and induce apoptosis. Inhibition of K (V) channels would thus attenuate PASMC apoptosis. |
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