Nitric oxide induces apoptosis by activating K+ channels in pulmonary vascular smooth muscle cells

Stefanie Krick, Oleksandr Platoshyn, Michele Sweeney, Sharon S. McDaniel, Shen Zhang, Lewis J. Rubin, Jason X.J. Yuan

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Nitric oxide (NO) is an endogenous endothelium-derived relaxing factor that regulates vascular smooth muscle cell proliferation and apoptosis. This study investigated underlying mechanisms involved in NO-induced apoptosis in human and rat pulmonary artery smooth muscle cells (PASMC). Exposure of PASMC to NO, which was derived from the NO donor S-nitroso-N-acetyl-penicillamine, increased the percentage of cells undergoing apoptosis. Increasing extracellular K+ concentration to 40 mM or blocking K+ channels with 1 mM tetraethylammonia (TEA), 100 nM iberiotoxin (IBTX), and 5 mM 4-aminopyridine (4-AP) significantly inhibited the NO-induced apoptosis. In single PASMC, NO reversibly increased K+ currents through the large-conductance Ca2+-activated K+ (Kca) channels, whereas TEA and IBTX markedly decreased the Kca currents. In the presence of TEA, NO also increased K+ currents through voltage-gated K+ (Kv) channels, whereas 4-AP significantly decreased the Kv currents. Opening of Kca channels with 0.3 mM dehydroepiandrosterone increased Kca currents, induced apoptosis, and further enhanced the NO-mediated apoptosis. Furthermore, NO depolarized the mitochondrial membrane potential. These observations indicate that NO induces PASMC apoptosis by activating Kca and Kv channels in the plasma membrane. The resulting increase in K+ efflux leads to cytosolic K+ loss and eventual apoptosis volume decrease and apoptosis. NO-induced apoptosis may also be related to mitochondrial membrane depolarization in PASMC.

Original languageEnglish (US)
Pages (from-to)H184-H193
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1 51-1
StatePublished - 2002
Externally publishedYes


  • Artery
  • Calcium
  • Mitochondrial membrane potential
  • Potassium current

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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