A fluorometric study of the possible role of calcium in synchronizing substrate metabolism with contractile performance in rabbit papillary muscle

Abstract

Based on the hypothesis that Ca2+ plays an important role in coordinating the rates of substrate catabolism with those of mechanical power utilization, experiments were designed to answer two questions. First, to what extent do the separate Ca2+ pools (e.g., Na+–Ca2+ exchange, sarcoplasmic reticulum (SR)) contribute to this messenger Ca2+ pool; and second, are the three catabolic pathways (glycolysis, β-oxidation, and tricarboxylic acid (TCA)) equally sensitive to regulation by Ca2+. To answer these questions, an assessment of the dynamic relation between metabolism and mechanical performance in rabbit papillary muscle was employed which used the slope (coupling coefficient: Mc) of the linear relation between the maximum oxidation of NADH accompanying an increase in contractile activity and the product of the peak isometric tension times the stimulation rate. Except for ketones, changes in superfusate [Ca2+] significantly decreased the coupling coefficient, suggesting a greater sensitivity of metabolism to mechanical requirement. Studies using ouabain indicated that this response was not attributable to Na+–Ca2+ exchange. Experiments with theophylline yielded two important results. First, the redox response of the respiratory chain can be significantly influenced by the available substrate. Second, the glycogenoltic complex associated with the SR may play an important role in ensuring adequate supplies of reducing equivalents and therefore may be a prime site for coordinating metabolism with mechanical performance. The data also suggest that glycolysis and β-oxidation are more sensitive to regulation by messenger Ca24 than the TCA cycle.