{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:02:36Z","timestamp":1791406956728,"version":"4.3.3"},"reference-count":60,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2012,7,15]]},"abstract":"<jats:p> In pulmonary arterial smooth muscle cells (PASMC), acute hypoxia increases intracellular Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) by inducing Ca<jats:sup>2+<\/jats:sup> release from the sarcoplasmic reticulum (SR) and Ca<jats:sup>2+<\/jats:sup> influx through store- and voltage-operated Ca<jats:sup>2+<\/jats:sup> channels in sarcolemma. To evaluate the mechanisms of hypoxic Ca<jats:sup>2+<\/jats:sup> release, we measured [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> with fluorescent microscopy in primary cultures of rat distal PASMC. In cells perfused with Ca<jats:sup>2+<\/jats:sup>-free Krebs Ringer bicarbonate solution (KRBS), brief exposures to caffeine (30 mM) and norepinephrine (300 \u03bcM), which activate SR ryanodine and inositol trisphosphate receptors (RyR, IP<jats:sub>3<\/jats:sub>R), respectively, or 4% O<jats:sub>2<\/jats:sub> caused rapid transient increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, indicating intracellular Ca<jats:sup>2+<\/jats:sup> release. Preexposure of these cells to caffeine, norepinephrine, or the SR Ca<jats:sup>2+<\/jats:sup>-ATPase inhibitor cyclopiazonic acid (CPA; 10 \u03bcM) blocked subsequent Ca<jats:sup>2+<\/jats:sup> release to caffeine, norepinephrine, and hypoxia. The RyR antagonist ryanodine (10 \u03bcM) blocked Ca<jats:sup>2+<\/jats:sup> release to caffeine and hypoxia but not norepinephrine. The IP<jats:sub>3<\/jats:sub>R antagonist xestospongin C (XeC, 0.1 \u03bcM) blocked Ca<jats:sup>2+<\/jats:sup> release to norepinephrine and hypoxia but not caffeine. In PASMC perfused with normal KRBS, acute hypoxia caused a sustained increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> that was abolished by ryanodine or XeC. These results suggest that in rat distal PASMC 1) the initial increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> induced by hypoxia, as well as the subsequent Ca<jats:sup>2+<\/jats:sup> influx that sustained this increase, required release of Ca<jats:sup>2+<\/jats:sup> from both RyR and IP<jats:sub>3<\/jats:sub>R, and 2) the SR Ca<jats:sup>2+<\/jats:sup> stores accessed by RyR, IP<jats:sub>3<\/jats:sub>R, and hypoxia functioned as a common store, which was replenished by a CPA-inhibitable Ca<jats:sup>2+<\/jats:sup>-ATPase. <\/jats:p>","DOI":"10.1152\/ajplung.00348.2011","type":"journal-article","created":{"date-parts":[[2012,5,12]],"date-time":"2012-05-12T05:00:18Z","timestamp":1336798818000},"page":"L161-L168","source":"Crossref","is-referenced-by-count":22,"title":["Ca<sup>2+<\/sup> responses of pulmonary arterial myocytes to acute hypoxia require release from ryanodine and inositol trisphosphate receptors in sarcoplasmic reticulum"],"prefix":"10.1152","volume":"303","author":[{"given":"Jian","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa A.","family":"Shimoda","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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