NERVOUS ACTION 



sheath. But such compounds are inactive if apphed to the axon. 

 The pecuUarity of the synapse in reacting to injected acetylcholine can 

 no longer be referred to a difference in the fundamental physicochemical 

 process underlying the propagation of the nerve impulse, but to the 

 difference in histological structure. This may also be the explanation 

 of Claude Bernard's famous curare experiment, since the active prin- 

 ciple of this compound is, according to recent investigations, a quater- 

 nary ammonium salt. 



Differences between Old and New Approaches 



The facts described here may suffice to illustrate the new ap- 

 proach and may be used for analysis of a few general aspects of the 

 problem. 



Loewi's discovery that a specific compound is released during 

 nerve activity was important and need not be minimized because of 

 the change in the original interpretation in the light of recent develop- 

 ments. Since the adoption of new methods led to.different conclusions, 

 the question appears of interest whether or not it is possible, with our 

 present knowledge, to find an explanation for the observations on which 

 the original conclusions and interpretations were based. 



In the older theories, it was assumed that acetylcholine is 

 liberated at the nerve ending and that, having crossed the synapse or 

 motor end plate, it acts directly on the effector cell or the second 

 neuron. Evidence for the role of acetylcholine as such a "neuro- 

 humoral" or "synaptic" transmitter was considered as satisfactory if the 

 following three effects could be produced: (1) a stimulating effect by 

 injected acetylcholine; (2) appearance of acetylcholine in the per- 

 fusion fluid following nerve stimulation; and (3) the enhancing effect 

 of eserine on nerve stimulation. 



The first effect is not necessarily physiological, but may well be 

 pharmacological. Other chemical compounds like nicotine or potas- 

 sium may have a similar effect. This would be, therefore, no conclu- 

 sive evidence for the assumption that acetylcholine is the mediator in 

 the original sense. Its appearance in the perfusion fluid following 

 nerve stimulation is a physiological event; this observation of Loewi 

 was significant because it connected the choline ester with nerve 

 activity. The mode of action, however, is not hereby explained. 

 Any compound forming j^art of an intracellular process may easily 



349 



