Cytochrome c activates K+ channels before inducing apoptosis

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

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)C1298-C1305
JournalAmerican Journal of Physiology - Cell Physiology
Volume283
Issue number4 52-4
DOIs
StatePublished - Oct 2002

Keywords

  • Apoptotic volume decrease
  • Pulmonary artery smooth muscle cells
  • Voltage-gated potassium channels

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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