Meeting Abstract
Muscle contraction is dependent on the release of Ca2+ from the sarcoplasmic reticulum (SR) followed by its binding to troponin-C (TnC), and relaxation requires the reuptake of Ca2+ by the SR, which drives its release from TnC. Quantitative analysis of this process requires detailed knowledge of the system components, which is often absent for comparative models. We therefore constructed a reaction-diffusion model of a fish white muscle sarcomere that comprised Ca2+ release, TnC binding, parvalbumin (Parv) binding, Ca2+ uptake, molecular diffusion and force production. We evaluated the sensitivity of force characteristics to these model components in an effort to define their functional ranges. The model compared well to force measurements in white muscle. Diffusion led to Ca2+ gradients along the sarcomere length that enhanced maximal force and generated a more rapid relaxation than the case where diffusion was infinitely fast. However, a modest increase in the sarcomere length or radius led to a decrease in maximal force. The model was highly sensitive to Ca2+ release and uptake. Lowering the release rate led to a lower maximal force, but increasing the rate led to only modest gains in maximal force while incurring much greater ATP costs associated with uptake, thus reducing contractile economy. Increasing the binding rate or concentration of Parv decreased maximal force but elevated rates of relaxation, and this effect was enhanced when Ca2+ uptake rates were lowered as may occur during fatigue. In general, these results show that a physiologically relevant set of parameters can be identified that lead to a functional sarcomere even when key experimental details are absent.
