Cytochrome c activates K+ channels before inducing apoptosis

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

Research output: Contribution to journalArticle

63 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume283
Issue number4 52-4
StatePublished - Oct 2002
Externally publishedYes

Fingerprint

Cytochromes c
Apoptosis
Mitochondria
Staurosporine
Dialysis
Caspase 9
Condensation
Chemical activation
Cells
Uridine Triphosphate
Vascular Smooth Muscle
Cytosol
Labeling
Smooth Muscle Myocytes
Muscle
Assays
Ions
Lung

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Cytochrome c activates K+ channels before inducing apoptosis. / Platoshyn, Oleksandr; Zhang, Shen; McDaniel, Sharon S.; Yuan, Jason.

In: American Journal of Physiology - Cell Physiology, Vol. 283, No. 4 52-4, 10.2002.

Research output: Contribution to journalArticle

Platoshyn, Oleksandr ; Zhang, Shen ; McDaniel, Sharon S. ; Yuan, Jason. / Cytochrome c activates K+ channels before inducing apoptosis. In: American Journal of Physiology - Cell Physiology. 2002 ; Vol. 283, No. 4 52-4.
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