STOCKDISC
Our present understanding of the mechanism of contraction is based on fundamental discoveries, all of which arose from studies on striated muscle as the early biochemists and physiologists became (naturally) interested in the basic question of how muscles generate movement. Much of the important work in this area took advantage of the beautiful, regular organization of muscle, as well as the abundance of material available for experimentation. The modern era began with the demonstration that contraction is the result of the interaction of ATP with two proteins, actin and myosin.
During the Second World War, and in complete scientific isolation in Szeged, Hungary, Albert Szent-Györgyi and colleagues established that the myosin originally described by Wilhelm Kühne in 1864 consisted of two proteins. The sole scientific instruments available to them were a simple Ostwald viscometer and polarizing filters to detect double refraction of flow. In 1942, Banga and Szent-Györgyi reported that exposure of ground muscle to a high salt concentration for 20 min led to the extraction of a protein of low viscosity, myosin A, whereas the protein extracted overnight, myosin B, had a high viscosity. Addition of ATP reduced the viscosity of myosin B, whereas the viscosity of myosin A remained essentially unaffected. In 1942, the effect of ATP on Kühne's myosin was independently discovered by Needham et al.
...many of the early milestones for the cytoskeleton field are the same as one would list if making a historical overview of the muscle field.
Margaret Titus
Szent-Györgyi found that the threads prepared from myosin B in physiological salt solutions shortened on addition of boiled muscle juice, whereas fibres of myosin A remained unchanged. The shortening was apparently due to the exclusion of water from the threads, and the active material in the boiled extract was identified as ATP. Straub joined Szent-Györgyi at about this time, and it became clear that the difference between myosin A and myosin B was due to the presence of another protein in the myosin B preparations, which they called actin. Straub purified actin, and showed that it increased the viscosity of myosin A and made it contractile. Straub also discovered that actin existed in two forms: in the absence of salt the actin was globular (G-actin), whereas in physiological salt concentrations the actin polymerized to form filaments (F-actin). Magnesium (Mg)activated the steady-state ATPase activity of myosin B (renamed actomyosin), but not that of myosin alone. In 1950, Straub and Feuer found that ATP was a functional group of G-actin, and that actin hydrolysed bound ATP when it polymerized. Subsequently, it was shown that actin polymerizes by a nucleation and elongation mechanism,and that non-muscle cells also contain actin.
However, it was the behaviour of the glycerol-extracted psoas muscle preparation described by Szent-Györgyi that provided conclusive evidence that the interaction of ATP with actomyosin was the basic contractile event. Upon addition of Mg-ATP, the preparation develops a tension that is comparable to that in living muscle. Moreover, the preparation behaves like actomyosin to some extent. The demonstration that contraction can be reproduced in vitro by two proteins, actin and myosin, opened up the modern phase of muscle biochemistry.
Soon afterwards, myosin was also isolated from non-muscle cells, followed by pioneering work on muscle contraction (see Milestone 3 and Milestone 9).
