Mechano-chemical coupling in spontaneous oscillatory contraction of muscle

Abstract

Muscle cells take either one of two states, namely contraction (on-state) and relaxation (off-state), under a particular physiological condition (physiological ionic strength, neutral pH and a few mM MgATP). The transition between these two states is regulated by micromolar concentrations of free Ca²⁺. Here we review spontaneous oscillation phenomena named SPOC. The SPOC state is attained in a contractile system of muscle (muscle model without cell membrane) as a third intermediate state. It appears either at an intermediate concentration of free Ca²⁺ (Ca-SPOC) or under the coexistence of MgATP with its hydrolytic products, i.e., MgADP and inorganic phosphate (Pi), where Ca²⁺ is not required (ADP-SPOC). We have constructed a three-dimensional Phase diagram showing three regions corresponding to three states of muscle realized under various concentrations of MgADP, Pi and free Ca²⁺ in the presence of MgATP; the SPOC region was sandwiched between contraction and relaxation regions. We tried to understand the mechano-chemical coupling in SPOC by explaining the mechanical properties of SPOC based on a standard kinetic scheme of actomyosin ATPase; the experimental results could be well simulated, except for the function of Pi, by assuming that a particular kinetic step regulated by Ca²⁺ is also regulated by the feed-back effect of the actomyosin-ADP complex. It is suggested that the SPOC state is attained by cyclic transition among the different chemical states of the actomyosin complex within each half-sarcomere, which occurs spontaneously through the mechanochemical coupling characteristic to the actomyosin complex, i.e., a mechano-enzyme.