VOL. 4 (1950) PERMEABILITY AND NERVE FUNCTION, I 93 



synapses may vary as to quantitative aspects. This is not surprising in view of the 

 discontinuity and other structural differences. Although the time relations are similar, 

 there is a synaptic delay of the order of a millisecond. This may be the result of several 

 factors, as e.g., the decreased diameter of the nerve fibre near the ending which may 

 lead to a decreased rate of conduction. Exact measurements of these various factors are 

 difficult, due to obvious technical reasons. However, the quantitative differences 

 between intracellular and transsynaptic propagation are well in the expected range, 

 and none of them requires the assumption of a fundamentally different mechanism. 



In conclusion, no convincing evidence exists supporting the idea that acetylcholine 

 assumes a function at the synapse entirely different from that in the axon, i.e. is released 

 from the nerve ending, penetrates the intercellular space and acts on the post-synaptic 

 membrane, thus substituting the flow of current as a "chemical mediator". A funda- 

 mental rule of scientific thinking requires that one should not assume two different 

 principles without necessity. Work and Work'^ have recently quoted the excellent 

 formulation of this rule by David Hume in his Treatise of Human Nature: "To invent 

 without scruple a new principle to every new phenomenon, instead of adapting it to 

 the old; to overload our hypothesis with a variety of this kind, are certain proofs, that 

 none of these principles is the just one, and that we only desire, by a number of false- 

 hoods, to cover our ignorance of the truth". Neither the so-called "electrical" nor the 

 "chemical" concept of synaptic transmission is satisfactory. The interpretation pro- 

 posed harmonizes both concepts by integrating the progress achieved concerning the 

 structure, the biochemical data and the electrical signs of activity. 



The earlier observations on acetylcholine deserve credit for having drawn the 

 attention of physiologists to this compound in connection with nerve activity. However 

 whereas, the ester was first associated with one type of nerve endings, then with a few 

 others, the study of its role by the combination of chemical and physical methods has 

 shown its essentiality in the conduction of nerve and muscle impulses throughout the 

 animal kingdom. The type of approach applied by Otto Meyerhof to studying muscular 

 contraction has proved valuable in obtaining a better understanding of fundamental 

 principles underlying the mechanism of another cellular function vital for life. 



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3 A. Krogh, Proc. Roy. Soc, B 133 (1946) 140. 



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10 R. D. Keynes, /. Physiol., 107 (1948) P. 



1^ M. A. RoTHENBERG AND E. A. Feld, /. Biol. Chem., 168 (1947) 223. 



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