In the field of the molecular mechanism of contraction in striated muscle, the stepwise progress was achieved by three great investigators in 1940's and 1950's.
Author: Haruo Sugi
Category: Muscle contraction
It is now widely recognized that fundamental progress in science is made not in a continuous manner but in a stepwise manner. In the field of the molecular mechanism of contraction in striated muscle, the stepwise progress was achieved by three great investigators in 1940's and 1950's. In the early 1940's, Albert Szent-Gyorgyi and his associates showed biochemically that muscle contraction is essentially an interaction between actin and myosin coupled with ATP hydrolysis. Then, in the 1950's, Hugh E. Huxley together with Jean Hanson demonstrated that striated muscle is composed of a hexagonal lattice of two kinds of interdigtating myofilaments consisting of action and myosin respectively, and made a monumental discovery that muscle contraction results from the relative sliding between the actin and myosin filaments. Andrew F. Huxley, who also participated in the discovery of the sliding filament mechanism of muscle contraction was attributed to the attachment-detachment cycle between the cross-bridges extending from the myosin filament and the complementary sites on the actin filament. After the above stepwise progress, however, muscle research appears to have entered into a period of so-called 'normal science' where detailed knowledge has been accumulating around the well established 'central dogmas' but without fundamental progress. More specifically, most experiments on muscle contraction mechanisms have been designed, carried out and interpreted on the basis of the Huxley's 1957 and the Huxley-Simmons' 1971 contraction models, as well as the kinetic scheme of actomyosin ATPase; but the molecular mechanism of contraction still remains to be a matter for debate and speculation. For further fundamental progress in this field of research, we feel it necessary to reconsider the validity of these dogmas and to interpret the results more freely. In 1978, one of us (H.S.) organized a symposium in Tokyo based on the above idea, and we published the proceedings under the title of "Cross-bridge Mechanism in Muscle Contraction" (ed. H. Sugi and G.H. Pollack, University of Tokyo Press/University Park Press, 1979). The unusual interest of muscle physiologists in this symposium encouraged us to organize a second symposium on muscle contraction in Seattle in 1982, and proceedings was again published under the title of "Contractile Mechanisms in Muscle" (ed. G.H. Pollack and H. Sugi, Plenum Publishing Corporation, 1984). We were again very much encouraged by the intense interest of the people at the symposium as well as by readers of the proceedings, and became convinced that the symposia of this kind would greatly accelerate the progress in this field. The present symposium was organized by one of us (H.S.) as the third "Cross-bride" symposium. Though most papers are concerned, as in the previous two symposia, with experiments on intact and demembranated muscle fibers and isolated myofibrils, where the three-Dimensional muofilament-lattice structures have been preserved, the results are frequently discussed in connection with the kinetics of actomyosin ATPase, reflecting the recent development of experimental methods connecting physiology and biochemistry. It has also become possible to obtain direct information about the orientation and configuration of the cross-bridges as various stages during muscle contraction.