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Am J Physiol Cell Physiol 283: C1298-C1305, 2002; doi:10.1152/ajpcell.00592.2001
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Vol. 283, Issue 4, C1298-C1305, October 2002

Cytochrome c activates K+ channels before inducing apoptosis

Oleksandr Platoshyn, Shen Zhang, Sharon S. McDaniel, and Jason X.-J. Yuan

Department of Medicine, University of California, San Diego, California 92103-8382

Cell shrinkage is an early prerequisite for apoptosis. The apoptotic volume decrease is due primarily to loss of cytoplasmic ions. Increased outward K+ currents have indeed been implicated in the early stage of apoptosis in many cell types. We found that cytoplasmic dialysis of cytochrome c (cyt-c), a mitochondria-dependent apoptotic inducer, increases K+ currents before inducing nuclear condensation and breakage in pulmonary vascular smooth muscle cells. The cyt-c-mediated increase in K+ currents took place rapidly and was not affected by treatment with a specific inhibitor of caspase-9. Cytoplasmic dialysis of recombinant (active) caspase-9 negligibly affected the K+ currents. Furthermore, treatment of the cells with staurosporine (ST), an apoptosis inducer that mediates translocation of cyt-c from mitochondria to the cytosol, also increased K+ currents, caused cell shrinkage, and induced apoptosis (determined by apoptotic nuclear morphology and TdT-UTP nick end labeling assay). The staurosporine-induced increase in K+ currents concurred to the volume decrease but preceded the activation of apoptosis (nuclear condensation and breakage). These results suggest that the cyt-c-induced activation of K+ channels and the resultant K+ loss play an important role in initiating the apoptotic volume decrease when cells undergo apoptosis.

apoptotic volume decrease; voltage-gated potassium channels; pulmonary artery smooth muscle cells


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