Activation of K+ channels induces apoptosis in vascular smooth muscle cells

Stefanie Krick, Oleksandr Platoshyn, Michele Sweeney, Hyong Kim, Jason Yuan

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Intracellular K+ plays an important role in controlling the cytoplasmic ion homeostasis for maintaining cell volume and inhibiting apoptotic enzymes in the cytosol and nucleus. Cytoplasmic K+ concentration is mainly regulated by K+ uptake via Na+-K+-ATPase and K+ efflux through K+ channels in the plasma membrane. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), a protonophore that dissipates the H+ gradient across the inner membrane of mitochondria, induces apoptosis in many cell types. In rat and human pulmonary artery smooth muscle cells (PASMC), FCCP opened the large-conductance, voltage- and Ca2+-sensitive K+ (maxi-K) channels, increased K+ currents through maxi-K channels [IK(Ca)], and induced apoptosis. Tetraethyl-ammonia (1 mM) and iberiotoxin (100 nM) decreased IK(Ca) by blocking the sarcolemmal maxi-K channels and inhibited the FCCP-induced apoptosis in PASMC cultured in media containing serum and growth factors. Furthermore, inhibition of K+ efflux by raising extracellular K+ concentration from 5 to 40 mM also attenuated PASMC apoptosis induced by FCCP and the K+ ionophore valinomycin. These results suggest that FCCP-mediated apoptosis in PASMC is partially due to an increase of maxi-K channel activity. The resultant K+ loss through opened maxi-K channels may serve as a trigger for cell shrinkage and caspase activation, which are major characteristics of apoptosis in pulmonary vascular smooth muscle cells.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume280
Issue number4 49-4
StatePublished - 2001
Externally publishedYes

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Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Large-Conductance Calcium-Activated Potassium Channels
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Chemical activation
Cells
Apoptosis
Pulmonary Artery
Valinomycin
Mitochondria
Ionophores
Cell membranes
Caspases
Cell Size
Ammonia
Cytosol
Adenosine Triphosphatases
Rats
Intercellular Signaling Peptides and Proteins

Keywords

  • Cytoplasmic calcium
  • Mitochondrial membrane potential
  • Pulmonary artery smooth muscle cells

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Activation of K+ channels induces apoptosis in vascular smooth muscle cells. / Krick, Stefanie; Platoshyn, Oleksandr; Sweeney, Michele; Kim, Hyong; Yuan, Jason.

In: American Journal of Physiology - Cell Physiology, Vol. 280, No. 4 49-4, 2001.

Research output: Contribution to journalArticle

Krick, Stefanie ; Platoshyn, Oleksandr ; Sweeney, Michele ; Kim, Hyong ; Yuan, Jason. / Activation of K+ channels induces apoptosis in vascular smooth muscle cells. In: American Journal of Physiology - Cell Physiology. 2001 ; Vol. 280, No. 4 49-4.
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