VOL. 4 (1950) PERMEABILITY AND NERVE FUNCTION, I 81 



the writer has tried to approach the problem of nerve metaboKsm in relation to function 

 in a way similar in principle to that which had proved so satisfactory and valuable in 

 the study of muscular contraction. It is a particular pleasure and privilege to pay tribute 

 to Professor Meyerhof at the occasion to which this volume is dedicated by reviewing 

 some aspects of this work. 



Role of Acetylcholine in Conduction 



Since the discovery of the powerful pharmacological effects of acetylcholine by 

 Reid Hunt and Taveau^' early in this century, the compound has attracted the 

 attention of physiologists. Observations of Magnus, Dale, Loewi, Cannon and many 

 others suggested that acetylcholine may be released from nerve endings and act as a 

 "mediator" of nerve impulse to the effector organ. There were many difficulties and 

 contradictions and the theory of chemical mediation encountered increasing opposition 

 (Fulton^^, Eccles^^). 



During the last 14 years the writer and his associates have offered evidence indi- 

 cating that the theory in its original form has to be modified. Based on the approach 

 outlined above, a great variety of facts have accumulated suggesting that the release 

 and removal of acetylcholine are intracellular processes^^^s^ They seem to be closely 

 associated with the alterations in the active membrane which occur during the passage 

 of the impulse. The transmitting agent is the flow of current but in the chain of events 

 which generate the "Stromchen" the acetylcholine-esterase system appears to play an 

 essential role. 



The important data have recently been summarized at a Symposium on the physio- 

 logical role of acetylcholine^^. A more detailed and comprehensive presentation may be 

 found in the textbook on Hormones^*. It may suf&ce to mention here briefly a few 

 essential facts, supporting the assumption of the necessity of acetylcholine in conduction. 

 Studies on the enzyme which hydrolyses acetylcholine, acetylcholine-esterase, have 

 revealed the following features: i. The reaction occurs at an extremely high rate, the 

 "turnover number" is 20000000 per minute or even higher, indicating that one molecule 

 of ester may be hydrolysed in 3-4 miUionth of a second^^ or possibly even faster (un- 

 published data) . This high speed is pertinent for any assumption correlating a chemical 

 reaction directly with the electrical manifestations of conduction. 2. Acetylcholine- 

 esterase is present in all conducting tissues throughout the whole animal kingdom^^. 27_ 

 3. The enzyme is localized exclusively in the surface where the bioelectrical phenomena 

 occur. This is in contrast to many other enzymes required for conduction, as for instance 

 the respiratory enzymes^. 4. The concentrations of the enzyme are adequate to account 

 for an amount of acetylcholine metabolized which is compatible with the assumption of 

 an essential role in conduction. 5. The enzyme in conducting tissues has a number of 

 properties by which it may be easily distinguished from other esterases occurring in 

 the organism^^' ^9. Only in erythrocytes the same type of esterase is found. Since the 

 physiological substrate is known to be acetylcholine, the use of the term acetylchohne- 

 esterase for this enzyme has been recently proposed^". 



All these features of acetylcholine-esterase, however suggestive, would not yet 

 permit the assumption of its essentiality for conduction. The enzyme activity has, 

 however, been correlated in many ways with the electrical events of conduction. In 

 experiments on the electric organ of Electrophorus electricns a direct proportionality has 

 been established between the voltage of the action potential and the concentration of 

 References p. 93I95. 

 6 



