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

Stefanie Krick, Oleksandr Platoshyn, Michele Sweeney, Hyong Kim, Jason X.J. Yuan

Research output: Contribution to journalArticle

142 Scopus citations

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)
Pages (from-to)C970-C979
JournalAmerican Journal of Physiology - Cell Physiology
Volume280
Issue number4 49-4
StatePublished - Jun 5 2001
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Fingerprint Dive into the research topics of 'Activation of K<sup>+</sup> channels induces apoptosis in vascular smooth muscle cells'. Together they form a unique fingerprint.

  • Cite this