VOL. 4 (1950) MYOSIN, ATP, AND MUSCLE CONTRACTION 43 



activity is very low around pn 74, the activity of fresh preparations increasing pro- 

 gressively up to and beyond p^ 10; Ca++ is an essential activator and Mg++ exercises 

 a strong antagonism to Ca++^. These facts have led Mommaerts and Seraidarian*, 

 to repudiate the possibility that ATP can break down in the fibre at more than a small 

 fraction of the rate required to produce the increase in free phosphate observed on 

 contraction. But here some recent experiments of Keilley and Meyerhof'' seem likely 

 to throw important light on a dark place. In a study of the ATPase activity of various 

 protein fractions from muscle, they found with myosin alone the high pn optimum and 

 the Ca++-Mg++ antagonism already mentioned; but with actomyosin (made from 

 ■"crystalline myosin" and purified actin) they observed in presence of Ca++ an optimum 

 activity around Ph T-T , almost unaltered by addition of Mg++. Szent-Gyorgyi^ had 

 already remarked on Mg++ activation of the ATPase activity of "impure natural 

 actomyosin" but this effect may have been due to presence of myokinase. Mommaerts 

 and Seraidarian^ report experiments on ATPase activity of actomyosin at p^ 7.0 

 and Ph 9.0 where Mg++ showed its antagonistic effect to Ca++. It certainly seems that 

 further enzymic examination of actin, myosin and their combinations might lead to 

 illuminating results. 



Keilley and Meyerhof' describe also the preparation from muscle of a second 

 Mg++-activated ATPase, p^ optimum 6.8, containing no myosin or actin, but possibly 

 ■associated with mitochondrial particles; this may correspond to the ATPase found in 

 the mitochondria of other tissues (Schneider^) but not yet so thoroughly investigated. 



It is clear from this study that it would be a difficult matter to specify at present 

 the optimal conditions for tne muscle ATPase activity. Further it has to be remembered 

 that there is considerable evidence (to be discussed later) for localization of materials 

 in the muscle fibre. This applies to the adenylic compounds and to inorganic salts, so 

 th^t we cannot assume that the ionic concentrations where the enzyme is acting in vivo 

 are the same as the overall ionic concentrations. Nor have we data from which to gauge 

 the extent of p^ variation within the fibre. 



the timing of ATPase activity in vivo and the effect of ATP on myosin 



We come now to the timing of the ATPase activity: does it occur simultaneously 

 with contraction or with relaxation? With this is bound up the whole question of the 

 details of interaction between myosin and ATP. Does ATP enter into combination with 

 myosin as a result of the stimulus or is it always in some kind of combination with some 

 part of the myosin chain ? Does the ATP in combining with the myosin act as a trigger 

 to set off the energy liberation and the shortening of the myosin ? Do tension develop- 

 ment and work performance depend on simultaneous ATP breakdown? Or does the 

 energy liberated in contraction come in the first place from energy stored in the myosin 

 chains, the energy from ATP dephosphorylation being used during relaxation to recon- 

 stitute the chains in their initial state? 



None of these questions can be answered with assurance. We shall consider briefly 

 the results obtained from experiments in vitro on the effect of ATP on myosin and 

 actomyosin since it is from further pursuit of such analytical procedures that we can best 

 hope to get a clue to the intimate mechanism of contraction. But at the present time 

 perhaps the best indication of an answer to any of these questions comes, not from any 

 results ifi vitro but from the fact that, in the living muscle, relaxation gives the impression 

 References p. 49. 



