Regulation of Muscle Contraction by Ca2+ and ADP: Focusing on the0 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.
KeywordsCardiac Muscle Thin Filament Sarcomere Length Myosin Head Optical Tweezer
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- Ebashi, S., Endo, M., and Ohtsuki, I., 1969, Control of muscle contraction, Quart. Rev. Biophys. 2:351–384.Google Scholar
- Endo, M., 1972a, Stretch-induced increase in activation of skinned muscle fibres by calcium, Nat. New Biol. 14:211–213.Google Scholar
- Endo, M., 1972b, Length dependence of activation of skinned muscle fibers by calcium, Cold Spring Harb. Symp. Quant. Biol. 37:505–510.Google Scholar
- Funatsu, T., Kono, E., Higuchi, H., Kimura, S., Ishiwata, S., Yoshioka, T., Maruyama, K., and Tsukita, S., 1993, Elastic filaments in situ in cardiac muscle: Deep-etch replica analysis in combination with selective removal of actin and myosin filaments, J. Cell Biol. 120:711–724.PubMedCrossRefGoogle Scholar
- Isambert, H., Venier, P., Maggs, A. C., Fattoum, A., Kassab, R., Pantaloni, D., and Carlier, M. F., 1995, Flexibility of actin filaments derived from thermal fluctuations. Effect of bound nucleotide, phalloidin, and muscle regulatory proteins, J. Biol. Chem. 270:11437–11444.PubMedCrossRefGoogle Scholar
- Ishiwata, S., 1975, Doctoral Thesis, Nagoya University. “Study on muscle proteins — Principally, dynamic properties of actin filament studied by quasielastic scattering of laser light.” pp. 229.Google Scholar
- Ishiwata, S., 1998, Use of fluorescent probes, in: Current Methods in Muscle Physiology-Advantages, Problems and Limitations-, H. Sugi, ed., Oxford Univ. Press, Oxford, pp. 199–222.Google Scholar
- Ishiwata, S., and Yasuda, K., 1993, Mechano-chemical coupling in spontaneous oscillatory contraction of muscle, Phase Transit. 45:105–136.Google Scholar
- Kinosita, K., Jr., Ishiwata, S., Yoshimura, H., Asai, H., and Ikegami, A., 1984, Submicrosecond and microsecond rotational motions of myosin head in solution and in myosin synthetic filaments as revealed by time-resolved optical anisotropy decay measurements, Biochemistry 23:5963–5975.CrossRefGoogle Scholar
- Ohtsuki, I., Masaki, T., Nonomura, Y., and Ebashi, S., 1968, Periodic distribution of troponin along the thin filament, J. Biochem. 61:817–819.Google Scholar
- Oosawa, F., Fujime, S., Ishiwata, S., and Mihashi, K., 1972, Dynamic property of F-actin and thin filament, Cold Spr. Harb. Symp. Quant. Biol. 37:277–285.Google Scholar
- Yasuda, K., Fujita, H., Fujiki, Y., and Ishiwata, S., 1994, Length regulation of thin filaments without nebulin, Proc. Jap. Acad. 70, Ser. B.:151–156.Google Scholar