{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:21:42Z","timestamp":1788175302085,"version":"build-2803163510"},"reference-count":31,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:p>We studied molecular and functional characteristics as well as hormonal regulation of the Na-K-2Cl cotransporter (NKCC) in the isolated rat heart and cardiomyocytes. NKCC activity was measured as bumetanide-sensitive<jats:sup>86<\/jats:sup>Rb<jats:sup>+<\/jats:sup>influx in isolated perfused rat hearts and isolated cardiomyocytes. Stimulation of \u03b1<jats:sub>1<\/jats:sub>-adrenoceptors (AR) by phenylephrine (30 \u03bcM) increased<jats:sup>86<\/jats:sup>Rb<jats:sup>+<\/jats:sup>influx. The NKCC inhibitor bumetanide (50 \u03bcM) reduced the response to phenylephrine by 45 \u00b1 13% ( n = 12, P &lt; 0.01). PD-98059 (10 \u03bcM), an inhibitor of the activation of the mitogen-activated protein kinases extracellular signal-regulated protein kinase 1 and 2 (ERK1\/2), reduced the total response to phenylephrine by 51 \u00b1 13% ( n = 10, P &lt; 0.01) and eliminated the bumetanide-sensitive component, indicating that \u03b1<jats:sub>1<\/jats:sub>-AR mediated stimulation of NKCC is dependent on activation of ERK1\/2. Inhibitors of protein kinase C or phosphatidylinositol 3-kinase had no effect. The presence of NKCC mRNA and protein was demonstrated in isolated rat cardiomyocytes. Phosphorylation of NKCC after \u03b1<jats:sub>1<\/jats:sub>-AR stimulation was shown by immunoprecipitation of the phosphoprotein from<jats:sup>32<\/jats:sup>P<jats:sub>i<\/jats:sub>prelabeled cardiomyocytes. Increased phosphorylation of the NKCC protein was also abolished by PD-98059. We conclude that the NKCC is present in rat cardiomyocytes and that ion transport by the cotransporter is regulated by \u03b1<jats:sub>1<\/jats:sub>-AR stimulation through phosphorylation of this protein involving the ERK pathway.<\/jats:p>","DOI":"10.1152\/ajpheart.00549.2003","type":"journal-article","created":{"date-parts":[[2004,3,12]],"date-time":"2004-03-12T18:52:56Z","timestamp":1079117576000},"page":"H1354-H1360","source":"Crossref","is-referenced-by-count":21,"title":["\u03b1<sub>1<\/sub>-AR-mediated activation of NKCC in rat cardiomyocytes involves ERK-dependent phosphorylation of the cotransporter"],"prefix":"10.1152","volume":"286","author":[{"given":"Geir 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