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Updated: May 29, 2026
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Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles
Published on: November 1, 2012
Sensitivity analysis of reaction-diffusion constraints in muscle energetics
S K Dasika1, S T Kinsey, B R Locke
1Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, 2525 Pottsdamer Street, Tallahassee, Florida 32310, USA.
Biotechnology and Bioengineering
|September 30, 2011
Summary
Skeletal muscle fibers function near a critical transition point between reaction and diffusion control. Key factors like ATPase rate, oxygen supply, and mitochondrial content determine this limit, impacting muscle performance across many animals.
Area of Science:
- Physiology
- Biophysics
- Biochemistry
Background:
- Skeletal muscle aerobic metabolism typically operates under reaction control.
- Some muscle fibers function near a transition point where diffusion control becomes significant.
- Understanding this transition is crucial for defining the limits of muscle function.
Purpose of the Study:
- To identify critical parameters influencing the switch from reaction to diffusion control in skeletal muscle metabolism.
- To define the parameter space governing this transition using sensitivity analysis.
Main Methods:
- A previously developed reaction-diffusion model was utilized.
- Sensitivity analysis (SA) was performed to assess the impact of various model parameters.
- Key parameters investigated included V(max,ATPase), O(2)⁰, ε(mito), and DO(2).
Main Results:
- The maximum rate for the ATPase reaction (V(max,ATPase)), capillary oxygen concentration (O(2)⁰), mitochondrial volume fraction (ε(mito)), and oxygen diffusion coefficient (DO(2)) are the most sensitive parameters.
- Muscle fibers avoid diffusion limitation with slow reactions (V(max,ATPase) < 25 mM/min), high oxygen supply (O(2)⁰ ≥ 35 µM), and substantial mitochondria (ε(mito) ≥ 0.1).
- Within the diffusion-controlled regime, oxygen diffusion significantly impacts metabolic rate and ATP levels more than other metabolites.
Conclusions:
- The transition between reaction and diffusion control is a key determinant of skeletal muscle function.
- Specific physiological conditions (low ATPase rate, high oxygen supply, ample mitochondria) prevent diffusion limitation.
- Oxygen diffusion is a critical factor influencing metabolic rate and ATP homeostasis in diffusion-limited muscle fibers.
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