Common Phenotype of Resting Mouse EDL and SOL Muscles: EDL

Common Phenotype of Resting Mouse EDL and SOL Muscles: Equal ATPase and Glycolytic Flux During Transient Anoxia

Model Status

This model describes the extensor digitorum longus muscle during resting state. It runs in PCEnv, COR and OpenCell to reproduce the original matlab, provided by the model authors. The units are consistent throughout.

Model Structure

ABSTRACT: Rates of ATPase and glycolysis are several times faster in actively contracting mouse extensor digitorum longus muscle (EDL) than soleus (SOL), but we find these rates are not distinguishable at rest. We use a transient anoxic perturbation of steady state energy balance to decrease PCr reversibly and to measure the rates of ATPase and of lactate production without muscle activation or contraction. The rate of glycolytic ATP synthesis is less than the ATPase rate, accounting for the continual PCr decrease during anoxia in both muscles. We fit a mathematical model validated with properties of enzymes and solutes measured in vitro and appropriate for the transient perturbation of these muscles to experimental data to test whether the model accounts for the results. Simulations showed equal rates of ATPase and lactate production in both muscles. ATPase controls glycolytic flux by feedback from its products. Adenylate kinase function is critical because rise in [AMP] is necessary to activate glycogen phosphorylase. ATPase is the primary source of H+ production. The sum of contributions of the thirteen reactions of the glycogenolytic and glycolytic network to total proton load is negligible. The stoichiometry of lactate and H+ production is near unity. These results identify a default state of energy metabolism for resting muscle in which there is no difference in the metabolic phenotype of EDL and SOL. Therefore additional control mechanisms, involving higher ATPase flux and [Ca++], must exist to explain for the well-known difference in glycolytic rates in fast-twitch and slow-twitch muscles in actively contracting muscle.

The original paper reference is cited below:

Common Phenotype of Resting Mouse EDL and SOL Muscles: Equal ATPase and Glycolytic Flux During Transient Anoxia, Kalyan Vinnakota, Joshua Rusk, Lauren Palmer, Eric Shankland and Martin J. Kushmeric, 2010, Journal of Physiology, Epub, 1-56. PubMed ID: 20308252