{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:16:04Z","timestamp":1792620964509,"version":"4.5.0"},"reference-count":41,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2016,6,1]]},"abstract":"<jats:p>Hypothermia\/rewarming (H\/R) is poorly tolerated by the myocardium; however, the underlying intracellular basis of H\/R-induced cardiac dysfunction remains elusive. We hypothesized that in cardiomyocytes, H\/R disrupts excitation-contraction coupling by reducing myofilament Ca<jats:sup>2+<\/jats:sup>sensitivity due to an increase in cardiac troponin I (cTnI) phosphorylation. To test this hypothesis, isolated rat cardiomyocytes (13\u201315 cells from 6 rats per group) were electrically stimulated to evoke both cytosolic Ca<jats:sup>2+<\/jats:sup>([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub>) and contractile (sarcomere shortening) responses that were simultaneously measured using an IonOptix system. Cardiomyocytes were divided into two groups: 1) those exposed to hypothermia (15\u00b0C for 2 h) followed by rewarming (35\u00b0C; H\/R); or 2) time-matched normothermic (35\u00b0C) controls (CTL). Contractile dysfunction after H\/R was indicated by reduced velocity and extent of sarcomere length (SL) shortening compared with time-matched controls. Throughout hypothermia, basal [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub>increased and the duration of evoked [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub>transients was prolonged. Phase-loop plots of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub>vs. contraction were shifted rightward in cardiomyocytes during hypothermia compared with CTL, indicating a decrease in Ca<jats:sup>2+<\/jats:sup>sensitivity. Using Western blot, we found that H\/R increases cTnI phosphorylation. These results support our overall hypothesis and suggest that H\/R disrupts excitation-contraction coupling of cardiomyocytes due to increased cTnI phosphorylation and reduced Ca<jats:sup>2+<\/jats:sup>sensitivity.<\/jats:p><jats:p>Listen to this article's corresponding podcast at http:\/\/ajpheart.podbean.com\/e\/hypothermiarewarming-disrupts-e-c-coupling\/ .<\/jats:p>","DOI":"10.1152\/ajpheart.00840.2015","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T04:16:30Z","timestamp":1458360990000},"page":"H1533-H1540","source":"Crossref","is-referenced-by-count":34,"title":["Hypothermia\/rewarming disrupts excitation-contraction coupling in cardiomyocytes"],"prefix":"10.1152","volume":"310","author":[{"given":"Niccole","family":"Schaible","sequence":"first","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young 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