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Gender modulation of Ca(2+) uptake in cardiac mitochondria.

Abstract：

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 Ca(2+) handling in rat cardiac mitochondria. METHODS:Using cardiac mitochondria isolated from male, female, and ovariectomized 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 Ca(2+) 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 Ca(2+) uptake in both substrate solutions when mitochondria from female and ovariectomized animals were compared to males, a finding consistent with gender modulation of the mitochondrial uniporter. Blockade of the Ca(2+) 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 Ca(2+) addition, 80% of female samples recovered from Ca(2+)-induced depolarization compared to 57% and 43% of male and ovariectomized animals, respectively. CONCLUSIONS:Mitochondria from female hearts have lower Ca(2+) uptake rates under physiologic substrate solutions (succinate/pyruvate) and are able to appropriately maintain DeltaYm under conditions of high [Ca(2+)]. These differences are consistent with gender modulation of the Ca(2+) uniporter and may be a mechanism by which female myocardium suffers less injury with ischemia/reperfusion.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Arieli Y,Gursahani H,Eaton MM,Hernandez LA,Schaefer S

doi

10.1016/j.yjmcc.2004.04.023

keywords:

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

507-13

issue

eissn

0022-2828

issn

1095-8584

pii

S0022282804001415

journal_volume

pub_type

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Gender modulation of Ca(2+) uptake in cardiac mitochondria.