Acute normoxia increases fetal pulmonary artery endothelial cell cytosolic Ca2+ via Ca2+-induced Ca2+ release

Raz Tirosh, Ernesto R. Resnik, Jean Herron, David J. Sukovich, Zhigang Hong, Edward K Weir, David N. Cornfield

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


To test the hypothesis that an acute increase in O2 tension increases cytosolic calcium ([Ca]i) in fetal pulmonary artery endothelial cells (PAECs) via entry of extracellular calcium and subsequent calcium-induced calcium release (CICR) and nitric oxide release, low-passage PAECs (<10 passages) were isolated from the intralobar pulmonary artery (PA) of fetal sheep and maintained under hypoxic conditions (Po2, 25 Torr). Using the calcium-sensitive dye fura-2, we demonstrated that acute normoxia (Po2 = 120 Torr) increased PAECs [Ca]i by increasing the rate of entry of extracellular calcium. In the presence of either ryanodine or 2-aminoethoxy-diphenylborate (2APB), normoxia did not lead to a sustained increase in PAECs [Ca]i Whole-cell patch clamp studies demonstrated that acute normoxia causes PAEC membrane depolarization. When loaded with the nitric oxide (NO)-sensitive dye, DAF - FM, acute normoxia increased PAEC fluorescence. In PAECs derived from fetal lambs with pulmonary hypertension, an acute increase in O2 tension had no effect on either [Ca]i or NO production. Hypoxia increases loading of acetylcholine-sensitive calcium stores, as hypoxia potentiated the response to acetylcholine We conclude that acute normoxia increases [Ca]i and NO production in normotensive but not hypertensive fetal PAECs via extracellular calcium entry and calcium release from calcium-sensitive intracellular stores.

Original languageEnglish (US)
Pages (from-to)258-263
Number of pages6
JournalPediatric Research
Issue number3
StatePublished - Sep 2006


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