Essential role of a Ca2+-selective, store-operated current (ISOC) in endothelial cell permeability determinants of the vascular leak site

Academic Article


  • Store-operated calcium (SOC) entry is sufficient to disrupt the extra-alveolar, but not the alveolar, endothelial cell barrier. Mechanism(s) underlying such insensitivity to transitions in cytosolic calcium ([Ca 2+]i) in microvascular endothelial cells are unknown. Depletion of stored Ca2+ activates a larger SOC entry response in extra-alveolar (pulmonary artery; PAECs) than alveolar (pulmonary microvascular; PMVECs) endothelial cells. In vivo permeation studies revealed that Ca 2+ store depletion activates similar nonselective cationic conductances in PAECs and PMVECs, while only PAECs possess the calcium-selective, store-operated Ca2+ entry current, I SOC. Pretreatment with the type 4 phosphodiesterase inhibitor, rolipram, abolished thapsigargin-activated ISOC in PAECs, and revealed ISOC in PMVECs. Rolipram pretreatment shifted the thapsigargin-induced fluid leak site from extra-alveolar to alveolar vessels in the intact pulmonary circulation. Thus, our results indicate ISOC provides a [Ca2+]i source that is needed to disrupt the endothelial cell barrier, and demonstrate that intracellular events controlling ISOC activation coordinate the site-specific vascular response to inflammation. © 2005 American Heart Association. Inc.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 9558400
  • Author List

  • Wu S; Cioffi EA; Alvarez D; Sayner SL; Chen H; Cioffi DL; King J; Creighton JR; Townsley M; Goodman SR
  • Start Page

  • 856
  • End Page

  • 863
  • Volume

  • 96
  • Issue

  • 8