VOL. 4 (1950) PRIMARY REACTION IN MUSCULAR ACTIVITY 5I 



signijEicance has been underlined by Meyerhof^i. If a muscle with parallel fibre arrange- 

 ment is kept in distilled water for a prolonged time, and is frozen and thawed, one 

 obtains a preparation which consists essentially of the original undisturbed fibrils, and 

 from which the soluble constituents of the sarcoplasma, including all factors which have 

 to do with irritability, have been removed. No stimulation will cause contraction of 

 these fibrils. They shorten, however, promptly if ATP in a proper electrolytic medium 

 is added. In this case there appears to be little doubt that ATP has directly acted upon 

 the contractile structure itself. 



The analysis has gone further. One can extract and fractionate the muscle, and 

 obtain a crystalline protein, myosin (Szent-Gyorgyi, I.e.) and supposedly pure actin 

 (Straub^^' 34). Combined with each other, they form the complex actomyosin which can 

 also be extracted directly (Szent-gyorgyi, I.e.) and from which threads may be spun. 

 These threads, suspended in the same solution of KCl and MgClo as is used with the fibril 

 preparation, will contract in response to the addition of ATP (Szent-Gyorgyi I.e.). 

 It is true that these threads, unhke fibrils, become shorter and thinner instead of thicker. 

 This is however merely a consequence of the fact that the actomyosin particles in such 

 a thread are very imperfectly orientated. After initial difficulties (Gerendas13),Buchthal 

 et al.^ have succeeded in preparing well orientated threads, and these behave in accor- 

 dance with the rule by becoming thicker during contraction. Two objections have been 

 made. Buchthal et al., at the International Congress of Physiology in Oxford (1947)^ 

 (repeated by Perry et al.^^) raised the difficulty that such threads, when loaded, do not 

 contract but become stretched upon addition of ATP. This may be due to the circum- 

 stance that in the formation of the threads very few and weak points of intermicellar 

 attachment are formed, which are not able to carry any strain. Since the action of ATP 

 upon actomyosin includes a disaggregative effect as well, the plasticity of the threads 

 is actually increased by ATP. In the fibrils on the other hand, very strong intermicellar 

 bonds exist in the densely packed system. The second objection, made by Astbury at 

 the Experimental Cytology Congress in Stockholm (1947) (Perry et al.^^), was that upon 

 electron-microscopical investigation actomyosin, after treatment with ATP at 0.05 M 

 KCl, 0.005 M MgClo, showed a dispersion of the original aggregates, with no indication 

 of a true contraction. Since however after the addition of ATP, during the drying of the 

 preparation, the salt concentration had to increase and pass the limit above which the 

 actomyosin dissolves and disaggregates, this experiment has no bearing upon the, 

 mechanism of contraction. Finally, the same authors^^, (p. 677) object that, even if the 

 shortening of actomyosin threads may imitate the contraction of muscle, these threads 

 show no relaxation. According to all we know about muscle, however, relaxation would 

 seem to be the more comphcated phenomenon. That this has not yet been reproduced 

 in vitro is no objection against a contribution relevant to contraction. The objection is 

 invalid the more so, since the contraction process in threads takes place to an extreme 

 extent. Such extreme shortenings are irreversible even in vivo (Ramsey's deltastate^i). 

 It seems thus that Szent-gyorgyi's observations on the effect of ATP upon actomyosin 

 are not subject to any serious inconsistency at this moment. 



A further simplification may be achieved by working not with carefully prepared 

 actomyosin threads, but with a suspension of finely precipitated actomyosin flocks. 

 Addition of ATP will cause their contraction as well. Since they are perfectly disoriented, 

 their contraction will take place in all dimensions equally. It is manifested by an 

 increased tendency of the flocks to settle (Szent-Gyorgyi's "superprecipitation"), and 

 References p. sSj^j. 



