Comprehensive Simulation of Ca Transients in the Continuum of Mouse Skeletal Muscle Fiber Types.

Mag-Fluo-4 has revealed differences in the kinetics of the Ca transients of mammalian fiber types (I, IIA, IIX, and IIB). We simulated the changes in [Ca] through the sarcomere of these four fiber types, considering classical (troponin -Tn-, parvalbumin -Pv-, adenosine triphosphate -ATP-, sarcoplasmic reticulum Ca pump -SERCA-, and dye) and new (mitochondria -MITO-, Na/Ca exchanger -NCX-, and store-operated calcium entry -SOCE-) Ca binding sites, during single and tetanic stimulation. We found that during a single twitch, the sarcoplasmic peak [Ca] for fibers type IIB and IIX was around 16 µM, and for fibers type I and IIA reached 10-13 µM. The release rate in fibers type I, IIA, IIX, and IIB was 64.8, 153.6, 238.8, and 244.5 µM ms, respectively. Both the pattern of change and the peak concentrations of the Ca-bound species in the sarcoplasm (Tn, PV, ATP, and dye), the sarcolemma (NCX, SOCE), and the SR (SERCA) showed the order IIB ≥ IIX > IIA > I. The capacity of the NCX was 2.5, 1.3, 0.9, and 0.8% of the capacity of SERCA, for fibers type I, IIA, IIX, and IIB, respectively. MITO peak [Ca] ranged from 0.93 to 0.23 µM, in fibers type I and IIB, respectively, while intermediate values were obtained in fibers IIA and IIX. The latter numbers doubled during tetanic stimulation. In conclusion, we presented a comprehensive mathematical model of the excitation-contraction coupling that integrated most classical and novel Ca handling mechanisms, overcoming the limitations of the fast- vs. slow-fibers dichotomy and the use of slow dyes.