In vivo modular control analysis of energy metabolism in contracting skeletal muscle
Résumé
We used 31P MR spectroscopy measurements of energetic intermediates (ATP, Pi, PCr) in combination with the analytical tools of metabolic control analysis to study in vivo energy metabolism in contracting skeletal muscle of anesthetized rats over a broad range of workload. According to our recent Modular Control Analysis (MoCA) used to describe regulatory mechanisms in beating heart, we defined the energetic system of muscle contraction as two modules (PCr-Producer and PCr-Consumer) connected by the energetic intermediates. Hypoxia and electrical stimulation were used in this in vivo study as reasonably selective modulations of Producer and Consumer respectively. As quantified by elasticity coefficients, the sensitivities of each module to PCr determine the control of steady state contractile activity and metabolite concentrations. The magnitude of the elasticity of the producer was high (4.3±0.6) at low workloads and decreased 5-fold (to 0.9±0.2) at high workloads. By contrast, the elasticity of the consumer remained low (0.5 to 1.2) over the range of metabolic rates studied. The control exerted by each module over contraction was calculated from these elasticities. The control of contraction was found on the consumer at low workloads then swung to the producer, due to the workload-dependent decrease in the elasticity of producer. The workload-dependent elasticity and control pattern of energy production in muscle is a major difference with heart. Since module rate and elasticity depend on the concentrations of substrates and products, the absence of homeostasis of the energetic intermediates in muscle, by opposition to heart, may likely be the origin of the workload-dependent elasticity of the producer module.
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