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 Ca2+ sensitivity due to an increase in cTnI phosphorylation. To test this hypothesis, isolated rat cardiomyocytes (13-15 cells from 6 rats per group) were electrically stimulated to evoke both cytosolic Ca2+ ([Ca2+]cyto2+]cyto increased and the duration of evoked [Ca2+]cyto transients was prolonged. Phase-loop plots of [Ca2+]cyto versus contraction were shifted rightward in cardiomyocytes during hypothermia compared to CTL indicating a decrease in Ca2+ sensitivity. Using Western blot, we found that H/R increases cardiac troponin I (cTnI) phosphorylation. These results support our overall hypothesis and suggest that H/R disrupts excitation-contraction coupling of cardiomyocytes due to increased TnI phosphorylation and reduced Ca2+ sensitivity.
- excitation-contraction coupling
- troponin I
- Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology