PRIMARY EVENT IN MUSCLE ACTION 



These factors are able to inhibit or reverse the mechanical re- 

 sponse (e.g., contraction) observed with the inodel alone, and 

 likewise to inhibit or enhance the ATPase activity of the system. 



Five such factors have to date been recognized : myokinase 

 (50), ATP-creatine transphosphorylase + creatine phos- 

 phate (28), pyrophosphate (17), "EDTA" or ethylene diamine 

 tetraacetate (16,69), and the arginine transphosphorylase sys- 

 tem (68). The third and fourth substances clearly upset what 

 might otherwise seem a good correlation between factor and 

 transphosphorylase activity; moreover, there is seemingly no 

 correlation between conditions promoting factor activity and 

 conditions promoting the usual activity of the transphosphory- 

 lases. Two common features which do seem significant, however, 

 are that (as first pointed out to us by Watanabe) these substances 

 all have a strong affinity for Mg++, and that they are all anionic 

 as used. There are also similarities in their behavior. (7) 

 Mg^"*" and ATP are both required by all factors. (2) In the 

 presence of Mg++ and ATP factors are tightly bound to myosin,* 

 most probably in cooperative fashion. (3) Ca+"'' can abolish 

 the action of all factors, and (4) increasing ionic strength and de- 

 creasing /?H appear to favor factor action. 



Of the five factors listed, at least the myokinase and ATP- 

 creatine transphosphorylase systems exist in mammalian muscles, 

 and the ATP-arginine transphosphorylase system exists in 

 pecten. It is therefore cogent to inquire how the operation of 

 these factors may complicate the experimentally observed be- 

 havior of the simple ATP-myosin-Mg system, for we think it is 

 this inquiry which may resolve present discrepancies between 

 models and muscles. Specifically, it seems possible that in 



* Students of the relaxation phenomenon reached this conclusion by 

 estimating ease of rinsing factor away. At least in the case of EDTA the 

 same conclusion was reached in another way. The investigations by Friess, 

 Bowcn, Kerwin, and one of us (13,25,27) on the activation of dissolved myosin 

 ATPase by EDTA indicate that EDTA exerts its effect by actually binding 

 on the myosin, that this binding occurs only when ATP is present, and that 

 in all probability this binding is mediated by Mg — possibly Mg which is an 

 integral part of the enzymatic site. 



623 



