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Cytochrome c activates K+ channels before inducing apoptosis.
Oleksandr Platoshyn1, Shen Zhang, Sharon S McDaniel
1Department of Medicine, UCSD Medical Center, University of California-San Diego, 200 W Arbor Drive, San Diego, CA 92103-8382, USA.
American Journal of Physiology. Cell Physiology
|September 13, 2002
Summary
Cytochrome c (cyt-c) rapidly increases potassium (K+) currents, initiating cell shrinkage and apoptosis. This K+ channel activation precedes nuclear changes, highlighting its role in early apoptotic volume decrease.
Area of Science:
- Cell Biology
- Molecular Biology
- Physiology
Background:
- Cell shrinkage is a key early event in apoptosis.
- Apoptotic volume decrease is primarily driven by cytoplasmic ion loss.
- Increased outward potassium (K+) currents are implicated in early apoptosis.
Purpose of the Study:
- To investigate the role of cytochrome c (cyt-c) in K+ current activation during apoptosis.
- To determine if K+ channel activation precedes or follows other apoptotic events.
- To elucidate the mechanism of cyt-c-induced apoptotic volume decrease.
Main Methods:
- Cytoplasmic dialysis of cyt-c in pulmonary vascular smooth muscle cells.
- Treatment with staurosporine (ST) to induce apoptosis.
- Measurement of K+ currents.
- Assessment of nuclear morphology and DNA fragmentation (TdT-UTP nick end labeling assay).
Main Results:
- Cytoplasmic cyt-c rapidly increased K+ currents, independent of caspase-9.
- Staurosporine treatment increased K+ currents, caused cell shrinkage, and induced apoptosis.
- The increase in K+ currents preceded nuclear condensation and breakage during staurosporine-induced apoptosis.
- K+ loss was concurrent with cell volume decrease.
Conclusions:
- Cyt-c-induced K+ channel activation is a critical early step in initiating apoptotic volume decrease.
- The rapid increase in K+ currents plays a significant role in the early stages of apoptosis.
- This mechanism highlights the importance of ion flux in programmed cell death.