6 A. V. HILL VOL. 4 (1950) 



"On the arrival of a nerve impulse, ATP is broken down, giving rise to ADP and 

 inorganic phosphate, furnishing at the same time the contraction energ}-. The ADP is 

 promptly converted again into ATP at the expense of phosphagen and no change in the 

 ATP content of the muscle can be detected ..." Others suppose that contraction is 

 associated with the formation of myosin — ATP and that ATP is broken down in relaxa- 

 tion. By Sandow^ a slight initial lengthening (in a muscle under tension) after a stimulus 

 ("latency relaxation") is attributed to the formation of a complex between activated 

 myosin and ATP. Most of this is pure speculation, without direct experimental evi- 

 dence. Unlike Mr. Stalin (Historicus^) I have no general theory of revolutions, 

 but I did once write an article (1932), which I think is still worth reading, on "The 

 Revolution in Muscle Physiology"^. That was after phosphagen had deposed lactic 

 acid from pride of place as the chief chemical agent in contraction. At that date 

 one could write: "On stimulation, phosphagen breaks down . . .: this is the primary 

 change by which energy is set free". Only four years earlier Ritchie^ wrote: "On 

 stimulation of a muscle fibre the wave of excitation passes down it; by increasing 

 the permeability of a membrane or by some other means it causes the liberation 

 of lactic acid from a carbohydrate source. The liberated hydrogen ions neutralize the 

 negative charge on a surface of protein, Meyerhof's V erkiirzungsort . . . and thereby 

 alter the type of structure, the area of surface, and the mechanical constants. This will 

 be the fundamental change." In the lactic acid era the evidence that the formation of 

 lactic acid was the cause and provided the eneigy for contraction seemed pretty good. 

 In the phosphagen era a similar attribution to phosphagen appeared even better 

 justified. Now, in the adenosinetriphosphate era lactic acid and phosphagen have been 

 relegated to recovery and ATP takes their place. Those of us who have lived through 

 two revolutions are wondering whether and when the third is coming. 



It may very well be the case, and none will be happier than I to be quit of revolu- 

 tions, that the breakdown of ATP really is responsible for contraction or relaxation: 

 but in fact there is no direct evidence that it is. Indeed, no change in the ATP has ever 

 been found in living muscle except in extreme exhaustion, verging on rigor. This is 

 explained by supposing that as soon as ATP is broken down into ADP and phosphate 

 it is promptly restored in the so-called "Lohmann reaction" at the expense of creatine 

 phosphate. 



ADP + CP -> ATP + C 



If this happens after each stimulus, then the smallness of the changes involved and 

 their quickness make it extremely difficult to gain any direct evidence on the subject. 

 In a single twitch, for example, the heat set free is about 3 millicaloiies per gram, 

 which would correspond to the liberation from ATP of 2.5-10"' g molecule of phosphate 

 per giam of muscle. To measure so small a change, reversed within the duration of a 

 single twitch, might well seem an impossible task. 



We should not, however, be so satisfied with the explanation of why no change in 

 ATP is ever found in living muscle that we cease to look for it : for another possibility 

 exists. The total energy available from all sources (lactic acid, phosphagen and ATP) 

 for the anaerobic phase of contraction is about i cal/g, corresponding to about 400 

 twitches. The total energy similarly available after poisoning with iodoacetate (from 

 phosphagen and ATP) is about 0.25 cal/g corresponding to about 100 twitches. From the 

 known amount of ATP present is muscle, the total energy it could provide by breaking 

 References p. 11. 



