Hydrogen peroxide-induced Ca2+ mobilization in pulmonary arterial smooth muscle cells

Mo Jun Lin, Xiao Ru Yang, Yuan Ning Cao, James S.K. Sham

Research output: Contribution to journalArticlepeer-review


Reactive oxygen species (ROS) generated from NADPH oxidases and mitochondria have been implicated as key messengers for pulmonary vasoconstriction and vascular remodeling induced by agonists and hypoxia. Since Ca2+ mobilization is essential for vasoconstriction and cell proliferation, we sought to characterize the Ca2+ response and to delineate the Ca2+ pathways activated by hydrogen peroxide (H 2O2) in rat intralobar pulmonary arterial smooth muscle cells (PASMCs). Exogenous application of 10 μM to 1 mM H2O 2 elicited concentration-dependent increase in intracellular Ca 2+ concentration in PASMCs, with an initial rise followed by a plateau or slow secondary increase. The initial phase was related to intracellular release. It was attenuated by the inositol trisphosphate (IP 3) receptor antagonist 2-aminoethyl diphenylborate, ryanodine, or thapsigargin, but was unaffected by the removal of Ca2+ in external solution. The secondary phase was dependent on extracellular Ca2+ influx. It was unaffected by the voltage-gated Ca2+ channel blocker nifedipine or the nonselective cation channel blockers SKF-96365 and La 3+, but inhibited concentration dependently by millimolar Ni 2+, and potentiated by the Na+/Ca2+ exchange inhibitor KB-R 7943. H2O2 did not alter the rate of Mn2+ quenching of fura 2, suggesting store- and receptor-operated Ca2+ channels were not involved. By contrast, H2O 2 elicited a sustained inward current carried by Na+ at -70 mV, and the current was inhibited by Ni2+. These results suggest that H2O2 mobilizes intracellular Ca2+ through multiple pathways, including the IP3- and ryanodine receptor-gated Ca2+ stores, and Ni2+-sensitive cation channels. Activation of these Ca2+ pathways may play important roles in ROS signaling in PASMCs.

Original languageEnglish (US)
Pages (from-to)L1598-L1608
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number6
StatePublished - Jun 2007


  • Inositol trisphosphate receptor
  • Nonselective cation channels
  • Pulmonary arteries
  • Ryanodine receptor
  • Sodium-calcium exchange

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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