Modulating factors of calcium-free contraction at low [MgATP]: a physiological study on the steady states of skinned fibres of frog skeletal muscle.

Abstract

Factors that modulate Ca(2+)-free contraction at low [MgATP] were examined by analysing steady tension development in skinned fibres of frog skeletal muscle. The commonly accepted bell-shaped relationship between steady tension and log (1/[MgATP]) was found to be highly susceptible to subtle experimental conditions at the higher [MgATP] side (right limb). The limb shifted to the right with increased fibre thickness, interrupted stirring of the bathing solution, increased temperature and fibre extension, although the effects of temperature and extension were marked only in thick fibres (cross-sectional area > 6000 microns 2). The shift of the right limb was reproduced by an addition of ADP to the bathing solution. These results, together with the extreme steepness of the right limb in thick fibres, suggest that a diffusion-dependent self-regenerative activation occurs in thick fibres in which ADP accumulation and ATP depletion positively feed back through further activation of the myofibrillar ATPase. Numerical simulation supported the hypothesis of the self-regenerative activation under poor diffusion conditions, and suggested that a small rise in temperature and fibre extension can trigger the self-regenerative process at the right limb. Consequently, ADP, temperature and fibre extension are deduced to be the primary potentiators of the activation at low [MgATP]. The high efficiency of ADP in shifting the limb suggests that the activating efficiency of the MgADP-bound actomyosin complex is higher than the nucleotide-free actomyosin complex.