In mechanically unloaded mouse LV slices, energy expenditure during shortening is driven by Ca2+ handling and basal metabolism, without residual cross-bridge cycling.
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Ca2+-driven energetics in unloaded slices should not change practice; leaves open translation to intact human hearts.
Left ventricular (LV) myocardial slices were isolated from murine hearts (300 microm thick) and were stimulated at 1 Hz without external load. Mean myocardial slice O(2) consumption (MVo(2)) per minute (mMVo(2)) without stimulation was 0.97 +/- 0.14 ml O(2).min(-1).100 g LV(-1) and mean mMVo(2) with stimulation increased to 1.80 +/- 0.17 ml O(2).min(-1).100 g LV(-1) in normal Tyrode solution. Mean DeltamVo(2) (the mMVo(2) with stimulation - the mMVo(2) without stimulation) was 0.83 +/- 0.12 ml O(2).min(-1).100 g LV(-1). There were no differences between mean mMVo(2) with and without stimulation in Ca(2+)-free solution. The increases in extracellular Ca(2+) concentrations up to 14.4 mM did not affect the mMVo(2) without stimulation but significantly increased the mMVo(2) with stimulation up to 140% of control. The DeltamMVo(2) significantly increased up to 190% of the control in a dose-dependent manner. In contrast, the shortening did not increase in a dose-dependent manner. Cyclopiazonic acid (CPA; 30 microM) significantly reduced the DeltamMVo(2) to 0.27 +/- 0.06 ml O(2).min(-1).100 g LV(-1) (35% of control). The combination of 5 mM 2,3-butanedione monoxime (BDM) and 30 microM CPA did not further decrease DeltamMVo(2). Although BDM (3-5 mM) decreased the DeltamMVo(2) by 28-30% of control in a dose-independent manner, 3-5 mM BDM decreased shortening in a dose-dependent manner. Our results indicate that the DeltamMVo(2) of mouse LV slices during shortening under mechanically unloaded conditions consists of energy expenditure for total Ca(2+) handling during excitation-contraction coupling, basal metabolism, but no residual cross-bridge cycling.
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Yamashita et al. (2004) studied this question.
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