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Altered cardiac mitochondrial Ca 2+ regulation during rewarming following hypothermia
Author(s) -
Wold Ragnhild M,
Han Young Soo,
Schaible Niccole,
Pabelick Christina M,
Tveita Torkjel,
Prakash Y S,
Sieck Gary C
Publication year - 2007
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.21.5.a582-b
Subject(s) - cytosol , hypothermia , mitochondrion , myocyte , medicine , biology , chemistry , endocrinology , andrology , biophysics , microbiology and biotechnology , biochemistry , enzyme
The mechanisms underlying rewarming shock (cardiac failure during rewarming from profound hypothermia) are not known. Increased myocardial Ca 2+ levels and altered mitochondrial ultrastructure have been reported. We hypothesized that mitochondrial buffering of cytosolic Ca 2+ contributes to cardiac dysfunction. Enzymatically‐dissociated rat cardiac myocytes loaded with Ca 2+ indicators fluo‐3 (cytosolic) and rhod‐2 (mitochondrial) were electrically stimulated (0.5 Hz) and visualized using real time confocal microscopy. Myocytes were cooled from 37 to 15 °C over 1h, maintained at 15 °C for 30min, and rewarmed over 1h back to 37 °C. Hypothermia increased baseline mitochondrial Ca 2+ (134% of normothermic control), which returned to control levels after rewarming. In contrast, rewarming elevated cytosolic Ca 2+ significantly compared to controls (126% vs. 94%). During hypothermia both cytosolic and mitochondrial peak Ca 2+ , time to peak, and time to 50% decay increased by 135%, 150% and 200%, respectively, but returned to control levels during rewarming. These data indicate that during hypothermia, mitochondria buffer cytosolic Ca 2+ , and during rewarming, mitochondrial Ca 2+ is redistributed to the cytosol, leading to continued elevation in cytosolic Ca 2+ . The temporary Ca 2+ overload in mitochondria may further affect subsequent energy production and myocyte function. Supported by Mayo Foundation Clinical Research grants, and NIH grants HL74309 and GM56686.