{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T10:45:58Z","timestamp":1772793958626,"version":"3.50.1"},"reference-count":49,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2013,1,1]]},"abstract":"<jats:p>Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase and cell survival were investigated in a cellular model of ischemia-reperfusion (I\/R)-induced injury and protection by ouabain-induced preconditioning (OPC). Rat neonatal cardiac myocytes were subjected to 30 min of substrate and coverslip-induced ischemia followed by 30 min of simulated reperfusion. This significantly compromised cell viability as documented by lactate dehydrogenase release and Annexin V\/propidium iodide staining. Total Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase \u03b1<jats:sub>1<\/jats:sub>- and \u03b1<jats:sub>3<\/jats:sub>-polypeptide expression remained unchanged, but cell surface biotinylation and immunostaining studies revealed that \u03b1<jats:sub>1<\/jats:sub>-cell surface abundance was significantly decreased. Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase-activity in crude homogenates and<jats:sup>86<\/jats:sup>Rb<jats:sup>+<\/jats:sup>transport in live cells were both significantly decreased by about 30% after I\/R. OPC, induced by a 4-min exposure to 10 \u03bcM ouabain that ended 8 min before the beginning of ischemia, increased cell viability in a PKC\u03b5-dependent manner. This was comparable with the protective effect of OPC previously reported in intact heart preparations. OPC prevented I\/R-induced decrease of Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase activity and surface expression. This model also revealed that Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase-mediated<jats:sup>86<\/jats:sup>Rb<jats:sup>+<\/jats:sup>uptake was not restored to control levels in the OPC group, suggesting that the increased viability was not conferred by an increased Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase-mediated ion transport capacity at the cell membrane. Consistent with this observation, transient expression of an internalization-resistant mutant form of Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase \u03b1<jats:sub>1<\/jats:sub>known to have increased surface abundance without increased ion transport activity successfully reduced I\/R-induced cell death. These results suggest that maintenance of Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase cell surface abundance is critical to myocyte survival after an ischemic attack and plays a role in OPC-induced protection. They further suggest that the protection conferred by increased surface expression of Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase may be independent of ion transport.<\/jats:p>","DOI":"10.1152\/ajpheart.00374.2012","type":"journal-article","created":{"date-parts":[[2012,10,20]],"date-time":"2012-10-20T05:46:31Z","timestamp":1350711991000},"page":"H94-H103","source":"Crossref","is-referenced-by-count":26,"title":["Modulation of cardiac Na<sup>+<\/sup>,K<sup>+<\/sup>-ATPase cell surface abundance by simulated ischemia-reperfusion and ouabain preconditioning"],"prefix":"10.1152","volume":"304","author":[{"given":"Aude","family":"Belliard","sequence":"first","affiliation":[{"name":"Department of Biochemistry, College of Medicine, University of Toledo, Toledo, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoann","family":"Sottejeau","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, University of Toledo, 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