NERVE METABOLISM AND FUNCTION = 

 A CRITIQUE OF THE ROLE OF ACETYLCHOLINE 



By R. W. Gerard 



Department of Physiology, The University of Chicago, Chicago, Illinois. 



INTRODUCTION 



Clearly, the acetylcholine system is the theme around which these 

 papers have been arranged. The various hypotheses as to its functional 

 significance, and especially the one regarding it as an essential com- 

 ponent in conduction in the nerve fiber, have proven most fertile in re- 

 search suggestions — witness the many studies here reported and the 

 animated discussion of them. Yet, I must close with the judg- 

 ment, on the basis of what has been said here, that this hypothesis has 

 now exhausted its usefulness. 



May I first offer, as evidence of my own long sympathy to the' view I 

 shall shortly be dissecting, a quotation or two from my early writings? 



"It remains to correlate this material [on heat and metabolism] with 

 some actual mechanism of conduction. The current view that activity 

 of one portion of a nerve fiber is the stimulus to the adjacent portion 

 and so along the entire fiber has much to support it, especially in the 

 form developed by Lillie. Recent evidence indicates that conduction 

 itself may be analyzed into two phases occurring repeatedly in succes- 

 sion. The first is an explosive type of chemical change in a portion 

 of the membrane surrounding the nerve fiber, and it leads, probably 

 by local potentials, to ion movements within the fiber, which constitute 

 the second phase. Local concentration of ions against an adjacent por- 

 tion of membrane initiates here the explosive change, and so on. Prob- 

 ably the ion movements are associated with only a small fraction of the 

 energy changes, and with the behavior of the membrane during and 

 after conduction" (P- 499^). 



"... In this way, it is obvious, a wave of electric and chemical change 

 must spread along the nerve fiber in both directions from the point first 

 stimulated. This is the nerve impulse, a propagated excitation. . . . 

 Certain steps in this development are hypothetical, and it must be 

 recognized that the picture has been simplified to a merest skeleton. 



* This paper is essentially as presented on February 9, 1946. Later developments of any kind 

 have not been introduced into the discussion. 



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