Nonlinear force-length relationship in the ADP-induced contraction of skeletal myofibrils.
The regulatory mechanism of sarcomeric activity has not been fully clarified yet because of its complex and cooperative nature, which involves both Ca(2+) and cross-bridge binding to the thin filament. To reveal the mechanism of regulation mediated by the cross-bridges, separately from the effect of Ca(2+), we investigated the force-sarcomere length (SL) relationship in rabbit skeletal myofibrils (a single myofibril or a thin bundle) at SL > 2.2 microm in the absence of Ca(2+) at various levels of activation by exogenous MgADP (4-20 mM) in the presence of 1 mM MgATP. The individual SLs were measured by phase-contrast microscopy to confirm the homogeneity of the striation pattern of sarcomeres during activation. We found that at partial activation with 4-8 mM MgADP, the developed force nonlinearly depended on the length of overlap between the thick and the thin filaments; that is, contrary to the maximal activation, the maximal active force was generated at shorter overlap. Besides, the active force became larger, whereas this nonlinearity tended to weaken, with either an increase in [MgADP] or the lateral osmotic compression of the myofilament lattice induced by the addition of a macromolecular compound, dextran T-500. The model analysis, which takes into account the [MgADP]- and the lattice-spacing-dependent probability of cross-bridge formation, was successfully applied to account for the force-SL relationship observed at partial activation. These results strongly suggest that the cross-bridge works as a cooperative activator, the function of which is highly sensitive to as little as <or=1 nm changes in the lattice spacing.
Shimamoto
Yuta
Y
Department of Physics, Faculty of Science and Engineering, Waseda University, Tokyo, Japan.
Kono
Fumiaki
F
Suzuki
Madoka
M
Ishiwata
Shin'ichi
S
D000244:Adenosine Diphosphate / Q000008:administration & dosage*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005246:Feedback / Q000502:physiology; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009210:Myofibrils / Q000187:drug effects / Q000502:physiology*; D017711:Nonlinear Dynamics; D011817:Rabbits; D013314:Stress, Mechanical
D000244:Adenosine Diphosphate; D002118:Calcium