The sensitivity of fast muscle contractile function to the major components of the sarcomere Ca2 +-cycling system

- Reaction-diffusion model of a sarcomere matched experimental force measurements.
- Steep concentration gradients were present, but diffusion did not limit contraction.
- Increases in Ca2 + release rate enhance force slightly, but are energetically costly.
- Effects of variation in the parameter set that defines a sarcomere are described.

A reaction-diffusion model of a muscle sarcomere was developed to evaluate the sensitivity of force characteristics to diffusion and Ca2+-cycling components. The model compared well to experimental force measurements. Diffusion led to Ca2+ gradients that enhanced maximal force and accelerated relaxation compared to when diffusion was infinitely fast. However, a modest increase in sarcomere length or radius led to a decrease in maximal force. Lowering the Ca2+ release rate caused a lower maximal force, but increasing the rate led to only modest gains in maximal force while incurring much greater ATP costs associated with reuptake. Greater parvalbumin binding rates decreased maximal force but enhanced relaxation, and this effect was magnified when Ca2+ uptake rates were lowered as may occur during fatigue. These results show a physiological set of parameters that lead to a functional sarcomere of known dimensions and contractile function, and the effects of parameter variation on muscle function.

128