Calcium and the role of motoneuronal doublets in skeletal muscle control

This work presents a novel structural model of skeletal muscle activation, providing a physiologically based account of frequency-dependent muscle responses like the catch-like effect. Numerous Ca2+ reservoirs within muscle fibers are considered, and a simplified analysis of the allocation of Ca2+ resources and the dynamics of calcium transport is proposed. The model correctly accounts for catch-like effects in slow and fast-twitch fibers during long-train stimulations and force-frequency relations in different muscle types. Results obtained from the model compare favorably to experiments showing that prolonged increases in force characteristic of the catch-like effect are not accompanied by sustained increases in free myoplasmic Ca2+. Also, in agreement with early experiments, the interspike interval in catch-inducing doublets is seen to be an important parameter for regulating the precise onset amplitude of the catch-like effect. This suggests that a plausible physiological function for the inclusion of doublets or the exclusion of individual spikes within a regular motor-neuronal spike-train is to rapidly bring skeletal muscles to predefined target forces according to prespecified motor programs in the central nervous system. This is a potentially very useful property directly mediated by the catch-like process modeled here. One further prediction of the model is that the slope of the frequency-tension profile of a given muscle is highly sensitive to changes in the efficiency and temporal characteristics of the dihydropyridine-ryanodine receptor complex. Interestingly, this is consistent with findings made on cardiac muscles, and might incidentally explain some instances of cardiac failure.