MECHANISM OF MUSCULAR CONTRACTION

To summarize, then: the contraction of striated muscle is brought about by some mechanism which generates a relative sliding force between the partly overlapping arrays of actin and myosin filaments. There is very strong evidence that cross-bridges projecting out from the myosin filaments, and carrying the adenosine triphosphatase and actin binding sites, are involved in the generation of this force in some cyclical process. However, it appears that the mechanism must satisfy two conflicting requirements: (i) that the force be produced as a result of a precisely determined set of structural changes in a protein complex consisting of actin, myosin, and other components, and be associated with the splitting of a molecule of adenosine triphosphate; (ii) that the force-generating mechanism can work equally well over a considerable range of side spacings between the actin and myosin filaments. Recent evidence suggests that these requirements may be satisfied in the following way: the actual force-generating structure is attached to the backbone of the myosin filaments by a linkage, 400 angstroms long, which has flexible couplings at either end; the force-generating structure can therefore attach itself to the actin filament, in a constant configuration, and undergo exactly the same structural changes and produce the same longitudinal force over a wide range of interfilament separations. The muscle structure is arranged so that the linkage is under tension, not compression, when a contractile force is being generated, and so the force can be transmitted without difficulty. It is suggested that the characteristic feature of the contraction mechanism may be a rigid attachment of the globular head of the myosin molecule to the actin filament and an active change in the angle of attachment associated with the splitting of adenosine triphosphate. The availability of purified preparations of head" subunits now opens up the problem to detailed attack."