Hypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 1 2016

Fingerprint

Rewarming
Excitation Contraction Coupling
Hypothermia
Cardiac Myocytes
Troponin I
Sarcomeres
Phosphorylation
Webcasts
Induced Hypothermia
Myofibrils
Myocardium
Western Blotting

Keywords

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

ASJC Scopus subject areas

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

Cite this

Hypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes. / Schaible, Niccole; Han, Young Soo; Hoang, Thuy; Arteaga, Grace; Tveita, Torkjel; Sieck, Gary C.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 310, No. 11, 01.06.2016, p. H1533-H1540.

Research output: Contribution to journalArticle

Schaible, Niccole ; Han, Young Soo ; Hoang, Thuy ; Arteaga, Grace ; Tveita, Torkjel ; Sieck, Gary C. / Hypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes. In: American Journal of Physiology - Heart and Circulatory Physiology. 2016 ; Vol. 310, No. 11. pp. H1533-H1540.
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