Regulation of muscle contraction by Ca²⁺ and ADP: Focusing on the auto-oscillation (SPOC)

A molecular motor in striated muscle, myosin II, is a non-processive motor that is unable to perform physiological functions as a single molecule and acts as an assembly of molecules. It is widely accepted that a myosin II motor is an independent force generator; the force generated at a steady state is usually considered to be a simple sum of those generated by each motor. This is the case at full activation (pCa <5 in the presence of MgATP); however, we found that the myosin II motors show cooperative functions, i.e., non-linear auto-oscillation, named SPOC (SPontaneous Oscillatory Contraction), when the activation level is intermediate between those of contraction and relaxation (that is, at the intermediate level of pCa, 5∼6, for cardiac muscle, or at the coexistence of MgATP, MgADP and inorganic phosphate (Pi) at higher pCa (>7) for both skeletal and cardiac muscles). Here, we summarize the characteristics of SPOC phenomena, especially focusing on the physiological significance of SPOC in cardiac muscle. We propose a new concept that the auto-oscillatory property, which is inherent to the contractile system of cardiac muscle, underlies the molecular mechanism of heartbeat. Additionally, we briefly describe the dynamic properties of the thin filaments, i.e., the Ca²⁺-dependent flexibility change of the thin filaments, which may be the basis for the SPOC phenomena. We also describe a newly developed experimental system named "bio-nanomuscle," in which tension is asserted on a single reconstituted thin filament by interacting with crossbridges in the A-band composed of the thick filament lattice. This newly devised hybrid system is expected to fill the gap between the single-molecule level and the muscle system.