Regulation Analysis of Contractile ATPase Flux in Skeletal Muscle

The [Ca2+] regulation of contractile ATPase flux, Jp, in skeletal muscle was analysed by computation of the Response RJpCa2+ for a 10 Hz range of electrical stimulation frequencies. Results of our analysis of the kinetic controls in ATP free energy metabolism in a network model of contracting muscle (J.A.L. Jeneson, H.V. Westerhoff and M.J. Kushmerick (2000) Am. J. Physiol.279, C813–C832) formed the basis for the computations of RJpCa2+. We found that neural regulation of sustained force generation via simple [Ca2+]cyto frequency encoding in the network was robust for frequencies up to 2 Hz. Above 2 Hz, however, this regulation design broke down because of a shift in contractile ATPase flux control from the Ca2+-sensitive contractile filaments to mitochondria with low Ca2+ sensitivity. The role of glyco(geno)lytic ATP production at high contraction workloads is discussed in the context of this result