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 journalArticle

Abstract

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
Volume292
Issue number6
DOIs
StatePublished - Jun 1 2007

Keywords

  • 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

Fingerprint Dive into the research topics of 'Hydrogen peroxide-induced Ca<sup>2+</sup> mobilization in pulmonary arterial smooth muscle cells'. Together they form a unique fingerprint.

  • Cite this