DAVID NACHMANSOHN AND IRWIN B. WILSON 



This and various other observations seemed to Hnk acetylchohne 

 action with the electric discharge. 



Further investigations revealed that the energy released by 

 phosphocreatine breakdown is adequate to account for the total 

 electric energy released by the action potential. It appeared 

 safe to assume that the breakdown of phosphocreatine would 

 not be associated directly with the generation of bioelectric poten- 

 tials, but would be used as in muscle for immediate rephosphoryla- 

 tion of ADP resulting from the breakdown of ATP. But in con- 

 trast to the situation in muscle, where ATP is assumed to be the 

 primary source of energy for the contractile process, it appeared 

 for many reasons unlikely that ATP hydrolysis would provide 

 the energy for the elementary process in conduction. It appeared 

 more likely that acetylcholine hydrolysis would precede that of 

 ATP and that ATP would be used in the recovery process as 

 energy source for the synthesis of acetylcholine. It has indeed 

 been demonstrated, in 1943, that ATP hydrolysis provides the 

 energy for the acetylation of choline (23). This result was of 

 interest for biochemistry in general. It was the first demonstra- 

 tion of the use of ATP energy outside the glycolytic cycle and the 

 first enzymatic acetylation achieved in a soluble system. The 

 observations opened the way for a study of the mechanism of 

 acetylation in general, which played such a role in recent de- 

 velopments. They, moreover, indicated that acetylcholine hy- 

 drolysis precedes that of ATP; they made it possible, in com- 

 bination with many other facts, to attribute to acetylcholine an 

 essential function in the primary events of conduction. A more 

 detailed account of these investigations on the chemical reactions 

 underlying nerve activity may be found in recent summaries 

 (18-22,50). Before discussing more recent trends, the picture 

 which has emerged as to the role of acetylcholine in the elemen- 

 tary process of conduction may be briefly outlined. 



ROLE OF ACETYLCHOLINE IN THE ELEMENTARY PROCESS OF 

 CONDUCTION 



Nerve impulses are propagated along nerve and muscle 

 fibers by small electric currents. The mechanism of the genera- 



632 



