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

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California School of Medicine, San Diego, California 92103 The balance between apoptosis and proliferation in pulmonary artery smooth muscle cells (PASMCs) is important in maintaining normal pulmonary vascular st...

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Published in:American journal of physiology. Lung cellular and molecular physiology 2001-10, Vol.281 (4), p.887-L894
Main Authors: Krick, Stefanie, Platoshyn, Oleksandr, McDaniel, Sharon S, Rubin, Lewis J, Yuan, Jason X.-J
Format: Article
Language:English
Subjects:
4-Aminopyridine - pharmacology
Apoptosis - drug effects
Apoptosis - physiology
Cells, Cultured
Enzyme Inhibitors - pharmacology
Fluorescent Dyes - pharmacokinetics
Humans
Ion Channel Gating - physiology
Membrane Potentials - physiology
Mitochondria - metabolism
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - metabolism
Patch-Clamp Techniques
Potassium - pharmacokinetics
Potassium Channel Blockers
Potassium Channels - physiology
Pulmonary Artery - cytology
Rhodamine 123 - pharmacokinetics
Staurosporine - pharmacology
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Summary:Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California School of Medicine, San Diego, California 92103 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. apoptosis; voltage-gated potassium channels; potassium loss; caspases; mitochondrial membrane potential depolarization
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.2001.281.4.l887