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Hypothermia/Rewarming Disrupts Excitation‐Contraction Coupling in Cardiomyocytes
Author(s) -
Schaible Niccole,
Han Young Soo,
Hoang Thuy,
Arteaga Grace,
Tvieta Torkjel,
Gary Sieck
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1290.19
Subject(s) - hypothermia , contraction (grammar) , sarcomere , myofilament , troponin i , medicine , chemistry , endocrinology , cardiology , myocyte , myocardial infarction
Hypothermia/Rewarming (H/R) is poorly tolerated by the myocardium; however, the underlying intracellular basis of H/R‐induced cardiac injury remains elusive. We hypothesized that in cardiomyocytes, H/R leads to contractile dysfunction primarily through reduced Ca 2+ sensitivity of the myofilaments. To test this hypothesis, isolated rat cardiomyocytes (13–15 cells from 6 rats per group) were electrically stimulated to evoke both cytosolic Ca 2+ ([Ca 2+ ] cyto ) and contractile (sarcomere shortening) responses that were simultaneously measured using an IonOptix system. These measurements were subjected to the following temperature protocols: 1) hypothermia (15°C) followed by rewarming (35°C) or 2) time‐matched control (35°C). Contractile dysfunction after H/R was indicated by reduced shortening velocity and reduced extent of shortening of sarcomere length (SL) compared to time‐matched controls. Throughout hypothermia, basal [Ca 2+ ] cyto increased and the duration of the evoked [Ca 2+ ] cyto transients was prolonged. Phase‐loop plots of [Ca 2+ ] cyto versus contraction in cells exposed to H/R indicate that Ca 2+ sensitivity of contraction is reduced. Consistent with decreased Ca 2+ sensitivity, we found that cardiac troponin I (cTnI) phosphorylation (measured by Western blot) increased after H/R. Our results support our overall hypothesis and suggest that reduced Ca 2+ sensitivity and increased cTnI phosphorylation contributes to the altered excitation‐contraction coupling of cardiomyocytes following H/R. The clinical importance of our results brings focus to Ca 2+ sensitivity as a plausible therapeutic target in treating patients exposed to accidental hypothermia. Support or Funding Information NIH Grant 5T32HL10535 (NSS)