Hypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes

Niccole Schaible, Young Soo Han, Thuy Hoang, Grace Arteaga, Torkjel Tveita, Gary Sieck

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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 cardiac troponin I (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+]cyto) and contractile (sarcomere shortening) responses that were simultaneously measured using anIonOptixsystem. Cardiomyocytes were divided into two groups:1) those exposed to hypothermia (15°C for 2 h) followed by rewarming (35°C; H/R); or2) time-matched normothermic (35°C) 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 [Ca2+]cytoincreased and the duration of evoked [Ca2+]cytotransients was prolonged. Phase-loop plots of [Ca2+]cytovs. contraction were shifted rightward in cardiomyocytes during hypothermia compared with CTL, indicating a decrease in Ca2+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 Ca2+sensitivity. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/hypothermiarewarming-disrupts-e-c-coupling/.

Original languageEnglish (US)
Pages (from-to)H1533-H1540
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume310
Issue number11
DOIs
StatePublished - Jun 2016

Keywords

  • Cardiomyocyte
  • Excitation-contraction coupling
  • Hypothermia
  • Rewarming
  • Troponin I

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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