Gender modulation of Ca2+ uptake in cardiac mitochondria

被引:53
作者
Arieli, Y
Gursahani, H
Eaton, MM
Hernandez, LA
Schaefer, S
机构
[1] Univ Calif Davis, Div Cardiovasc Med, Davis, CA 95616 USA
[2] Dept Vet Affairs, Cardiol Sect, No Calif Hlth Care Syst, Sacramento, CA 95655 USA
关键词
estrogen; myocardium; calcium; mitochondria; gender; redox; NADH;
D O I
10.1016/j.yjmcc.2004.04.023
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Mitochondrial calcium overload is an important factor in defining ischemia/reperfusion injury. Since pre-menopausal women are relatively protected from ischemia and heart disease, we tested the hypothesis that gender differences alter Ca2+ handling in rat cardiac mitochondria. Methods: Using cardiac mitochondria isolated from male, female, and ovariectornized Sprague-Dawley rats, we measured mitochondrial calcium transport, redox state, and membrane potential (Deltapsi(m)) during exposure to a calcium bolus. Redox state was modulated using either succinate (S) or succinate and pyruvate (SP) as substrates. Results: Net Ca2+ uptake rates were significantly lower in female than male mitochondria using SP, substrate conditions that resulted in a lower redox state (NADH/NAD'). Inhibition of the mitochondrial transition pore (MTP) using cyclosporin A showed significantly lower net Ca2+ uptake in both substrate solutions when mitochondria from female and ovariectornized animals were compared to males, a finding consistent with gender modulation of the mitochondrial uniporter. Blockade of the Ca2+ uniporter by ruthenium red abolished gender or substrate solution differences in calcium release. While there were no significant differences in resting Deltapsi(m) or Deltapsi(m) following Ca2+ addition, 80% of female samples recovered from Ca2+-induced depolarization compared to 57% and 43% of male and ovariectornized animals, respectively. Conclusions: Mitochondria from female hearts have lower Ca2+ uptake rates under physiologic substrate solutions (succinate/pyruvate) and are able to appropriately maintain Deltapsim under conditions of high [Ca2+]. These differences are consistent with gender modulation of the Ca2+ uniporter and may be a mechanism by which female myocardium, suffers less injury with ischemiaJreperfusion. (C) 2004 Published by Elsevier Ltd.
引用
收藏
页码:507 / 513
页数:7
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