Energetic modulation of cardiac inotropism and sarcoplasmic reticular Ca2+ uptake.
Energetic modulation of cardiac inotropism and sarcoplasmic reticular Ca2+ uptake.
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DOI：
10.1016/0167-4889(94)90109-0
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发表时间：
1994-10
期刊：
影响因子：
--
通讯作者：
R. Mallet;R. Bünger
中科院分区：
文献类型：
--
作者：
R. Mallet;R. Bünger
Myocardial contractile performance is a function of sarcoplasmic reticular Ca 2+ uptake and release, Ca 2+ handling is ATP-dependent and can account for up to 40% of total myocardial energy expenditure. We tested the hypothesis that the thermodynamics of the cytosolic adenylate system can modulate sarcoplasmic reticular Ca 2+ handling and hence function in intact heart. Cellular energy level was experimentally manipulated by perfusing isolated working guinea-pig hearts with substrate-free medium or media fortified with lactate and/or pyruvate as the main energy substrate. Left ventricular contractile function was judged by stroke work and intraventricular d P d t. Cytosolic energy level was indexed by measured creatine kinase reactants. Relative to 5 mM lactate, 5 mM pyruvate increased left ventricular stroke work, d P d t max, and d P d t min, while lowering left ventricular end-diastolic pressure at physiological left atrial and aortic pressures. Pyruvate also doubled cytosolic phosphorylation potentials and increased [ATP][ADP] ratio; this energetic enhancement distinguishes pyruvate from inotropic stimulation by catecholamines, which are known to decrease cytosolic energy level in perfused heart. Sarcoplasmic reticular Ca 2+ handling was assessed in hearts prelabeled with 45 Ca, subjected to 45 Ca washout in the presence of different cytosolic energy levels, then stimulated with 10 mM caffeine to release residual sarcoplasmic reticular 45 Ca. When ryanodine (1 μM) was applied to open Ca 2+ channels and thereby released 45 Ca from the sarcoplasmic reticulum during washout, caffeine-stimulated 45 Ca release was decreased 96%, demonstrating that virtually the entire caffeine-sensitive 45 Ca pool was located in the sarcoplasmic reticulum. In detailed comparisons of pyruvate-energized vs. substrate-free deenergized hearts, an inverse relationship between cytosolic energy level and caffeine-mobilized 45 Ca pool size was observed. Thus, caffeine-induced 45 Ca release was decreased 60% by pyruvate energization and increased 2.5-fold by substrate-free deenergization. Taken together, these results support the hypothesis that enhancement of myocardial inotropism by energy-yielding substrate is mediated by increased sarcoplasmic reticular Ca 2+ loading/release. Thus we propose that the known control of sarcoplasmic reticular Ca 2+ turnover by the protein kinase/phospholamban system can be modulated by cytosolic energy level.
