PRIMARY EVENT IN MUSCLE ACTION 



The abstract features of our "plausible" theory are these: 

 It is supposed that the basic contractile element is a flexible 

 molecular chain which for certain reasons would — in the ab- 

 sence of the next stipulation — be considerably curled at equilib- 

 rium. It is further supposed, however, that fixed along the 

 chain are discrete electrical charges. The mutual repulsion 

 generally existing among these charges introduces an extensile 

 force preventing complete contraction of the chain. Under 

 these circumstances, varying the number of fixed charges will 

 vary the linear dimensions of the chain.* Application of these 

 notions to the myosin-ATP system is unstrained. It is very 

 likely that the basic elements of fibrous myosin, viz., its poly- 

 peptide chains, are intrinsically capable of curling. It is also 

 known that even "on the average" myosin is rich in polar resi- 

 dues, and recent indications that myosin is spatially hetero- 

 geneous only assure that certain regions of myosin will be 

 especially dense in electrical charge. Therefore, it is not hard 

 to imagine that its electrical charge keeps a myosin system ex- 

 panded far beyond its uncharged equilibrium shape. To in- 

 troduce a mechanism of altering the electrical charge on myosin 

 we have to recall two properties of ATP, viz., that it is itself a 

 highly charged anion {ca. 4— charge in neutral solution), and 

 that it is — as Engelhardt showed (20) — a substrate for the en- 

 zymatic activity of myosin. If one accepts the Michaelis theory 



* The operating principles used in this theoretical model are well known, 

 and in fact underlie the modern theory of polyelectrolytes. In reference to 

 muscle action, Wohlisch (73), Guth (30), and Bull (18) early pointed out that a 

 "certain reason" why a single molecular chain left to itself in a structureless, 

 inert medium would be curled is that a greater configurational entropy is 

 associated with moderate curling than with full extension. Likewise, Meyer 

 (51) early saw the mechanical implications of electrical fields arising from the 

 abundant ionized groups of myosin. The first conceptual synthesis of these 

 two principles into the model just described was due to Riseman and Kirkwood 

 (64) ; it was also these authors who first proposed that ATP changed the 

 charge on the myosin, but by a mechanism quite different from that to be 

 proposed here. The practical realization of the model was soon thereafter 

 achieved by Kuhn, Katchalsky, and their associates (42,45). 



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