Key result
Simulations using the full SR pump model demonstrated that the Michaelis-Menten approximation underestimates initial calcium binding and release while overestimating the later rate of calcium pumping.
A newly developed full SR pump model provides more accurate simulations of calcium transients in skeletal muscle than the traditional Michaelis-Menten approximation by accounting for fast initial binding.
Full SR pump model improves simulation accuracy in animal studies; leaves open any clinical translation to human muscle function.
The models of the sarcoplasmic reticulum (SR) Ca pump used to simulate Ca kinetics in muscle fibers are simple but inconsistent with data on Ca binding or steady-state uptake. We develop a model of the SR pump that is consistent with data on transient and steady-state Ca removal and has rate constants identified under near-physiological conditions. We also develop models of the other main Ca-binding proteins in skeletal muscle: troponin C and parvalbumin. These models are used to simulate Ca transients in cut fibers during and after depolarizing pulses. Simulations using the full SR pump model are contrasted with simulations using a Michaelis-Menten (MM) approximation to SR pump kinetics. The MM pump underestimates the amount of Ca released during depolarization, underestimates the initial rate of Ca binding by the pump, and overestimates the later rate of Ca pumping. These errors are due to fast initial binding by the SR pump, which is neglected in the MM approximation.
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Getz et al. (1997) studied Skeletal muscle calcium kinetics. Full sarcoplasmic reticulum (SR) pump model vs. Michaelis-Menten (MM) approximation was evaluated on Calcium transients in cut fibers during and after depolarizing pulses. Simulations using the full SR pump model demonstrated that the Michaelis-Menten approximation underestimates initial calcium binding and release while overestimating the later rate of calcium pumping.
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