Mitochondrial calcium content in isolated perfused heart: effects of inotropic stimulation.
We tested the hypothesis that in the intact heart, mitochondrial metabolism is activated by mitochondrial Ca2+ uptake during increased work. We measured left ventricular pressure (LVP), pyruvate dehydrogenase (PDH) activity, and mitochondrial and A band elemental content by electron probe microanalysis (EPMA) in Langendorff-perfused hamster hearts under control conditions, after isoproterenol (10(-6) M) stimulation, and after increasing perfusion pressure from 60 to 100 mmHg. Hearts were rapidly frozen, then EPMA was performed on cryosections cut from the surface of the frozen hearts; PDH activity was measured from the same area. Isoproterenol and elevated perfusion pressure increased LVP by 185 +/- 21 and 58 +/- 14%, respectively, versus controls. PDH activity increased from 10.4 +/- 1.5 (mean +/- SE) nmol.min-1. mg protein-1 (controls) to 21.6 +/- 3.5 (isoproterenol) and 18.5 +/- 3.2 nmol.min-1.mg protein-1 (increased perfusion pressure). There was no significant change in mitochondrial Ca1 in response to isoproterenol [1.2 +/- 0.1 (mean +/- SE) mmol/kg dry wt] or increased perfusion pressure (1.1 +/- 0.1) versus controls (1.0 +/- 0.1). These results suggest that, in the intact heart, mechanisms other than mitochondrial Ca2+ uptake may contribute to PDH activation and increased cardiac work.
Moravec
C S
CS
Center for Anesthesiology Research, Cleveland Clinic Foundation, Ohio 44195, USA.
Desnoyer
R W
RW
Milovanovic
M
M
Schluchter
M D
MD
Bond
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D003971:Diastole; D004577:Electron Probe Microanalysis; D005615:Freezing; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008929:Mitochondria, Heart / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D013599:Systole; D016277:Ventricular Function, Left
D011768:Pyruvate Dehydrogenase Complex; D007545:Isoproterenol; D002118:Calcium