VOL. 4 (1950) PERMEABILITY AND NERVE FUNCTION, I 89 



has changed. The demonstration of the release of acetylchoHne in the axon appears 

 as relevant as that at the synaptic junction and requires a modification of the original 

 interpretation. 



The structural barrier for acetylcholine present in the fibre and its absence in the 

 post-synaptic membrane may be considered as the main reason that the attention of 

 many physiologists was focused for such a long time on the synapse only. Very little 

 is known concerning the properties of the barrier and the factors affecting it. The 

 observations on the permeability of neuronal surface membranes described in this and 

 the following paper are only an initial phase in the attempt of analysing the problem. 

 Its importance can hardly be overemphasized, not only for the understanding of the 

 cellular mechanism but of the pharmacology and pathology of the nervous system as 

 well. The development of new drugs may be greatly facilitated if the structural factors 

 determining the permeability and the rate of penetration are known. In many cases an 

 action may be desirable, preferably or exclusively, on the synapse, in others, upon both 

 axon and synapse. 



The existence of structural barriers and the great variations of their properties 

 may account for the many obstacles encountered and the many contradictory reports 

 when the two criteria of chemical mediation were applied to different types of synapses. 

 The unnumerable differences of anatomical structure, the biochemical composition of 

 the surrounding medium and many other accessory conditions must be essential in 

 determining the action of acetylcholine when applied externally. These variations do 

 not permit the assumption that the fundamental physico-chemical mechanism of the 

 propagation of the nerve impulse may not be the same. In view of the physico-chemical 

 properties of acetylcholine and similar N-methylated compounds, the difficulties will 

 become nearly insurmountable in the study of brain and spinal chord which contain 

 large amounts of lipid. It is not surprising that the painstaking efforts to demonstrate 

 or to disprove the "cholinergic" nature of synapses .in brain and spinal chord have 

 resulted in a most unsatisfactory and confusing picture. 



In contrast the conflicting results obtained when the "cholinergic" nature of 

 synapses, especially in brain, is tested by the usual criteria of chemical mediation, the 

 approach based on the study of the enzymes connected with acetylcholine metabolism 

 and their correlation with function did not encounter comparable difficulties. All 

 results obtained in this way indicate the generality of the role of acetylcholine in all 

 conducting tissues, including that of brain and spinal chord^^. 



c) Basic similarity between conduction and transmission. At the Symposium on the 

 synapse, in 1939, Erlanger^* scrutinized the problem whether the electrical charac- 

 teristics of synaptic transmission are basically different from those which may be 

 observed on the axon. His data indicate that the electrical phenomena considered to be 

 pecularities of the synapse may be demonstrated on fibres, z;z^., latency, one-way trans- 

 mission, repetition, temporal summation and facilitation, and transmission of the action 

 potential across a non-conducting gap. The facts based on the electrical signs of nerve 

 activity make it unnecessary to assume that any condition exists at the synapse which 

 differs in principle from that found in the peripheral axon, except in quantitative respect. 



Ten years have passed. During that time extensive investigations have been made 

 on the electrical characteristics of tranrmission across the natural and artificial synapse 

 (ephapse). From the work of many investigators, mainly Arvanitaki^^' ^^, Bullock^^ 

 EccLES^^, Granit and Skoglund^ and others considerable evidence has accumulated 

 References p. 9 3(9 5. 



