PRIMARY EVENT IN MUSCLE ACTION 



is increased from zero the fiber will progressively shorten, that 

 at a critical value of the concentration the fiber will shorten dis- 

 continuously to a very reduced length, and then that as the con- 

 centration is further increased the fiber will again progressively 

 shorten. The discontinuity in the length-concentration curve 

 reflects 3. phase transition, that is to say, at the critical concentration 

 (and only at this concentration) two separate phases can coexist, 

 and are in equilibrium with one another. In the first case the 

 two phases correspond to two (myosin chain) -(solvent) mixtures 

 of different composition ; in the second case, to chains with pre- 

 dominantly intra-chain H-bonding and to chains with pre- 

 dominantly inter-chain H-bonding. The effect of a phase 

 transition is to exaggerate the dimensional changes in the 

 operation of the model, and also to introduce a critical condition 

 (e.g., ATP concentration) ; this last may be the basis of the 

 "razor-edge" character of muscle contraction. 



The foregoing theoretical model of the Engelhardt-Weber- 

 Szent-Gyorgyi experiments is simple enough, and sufficiently 

 understandable in straightforward physicochemical terms to 

 invite diversified experimental test. We shall next consider 

 three general lines of test. 



Following Engelhardt's discovery that myosin was an 

 ATPase, the idea that ATP might participate in the primary 

 event of muscle action gained wide acceptance because ATP has 

 long been considered an "energy-rich" compound, i.e., its hy- 

 drolysis has been thought to be highly exergonic and exothermic 

 (49). It has not been unreasonable, for example, to suppose 

 that ATP transfers its third phosphate to myosin, and that this 

 phosphorylated myosin is for some reason a contracted struc- 

 ture ; indeed much of Weber's elegant experimentation can, at 

 first sight, be so interpreted (70,71). Such a hypothesis asserts, 

 in essence, that contraction is coupled with hydrolytic cleavage, 

 and since in the absence of enzyme this cleavage is very exer- 

 gonic, the hypothesis seems further strengthened. By the same 

 token the theory expounded here frequently meets spirited, 

 albeit intuitive, resistance because it implies a major free-energy 



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