16 DAVID P. C. LLOYD 



it is well to digress to take cognizance of the Gaskell effect (1887) for it is 

 probably to be considered the model for much that is discussed today in 

 relation to inhibition. Gaskell demonstrated during vagal stimulation an 

 increase in the demarcation current between normal and damaged regions 

 of the resting tortoise auricle, which is to say anelectrotonus. 



One wonders how it was that Keith Lucas failed to consider, along with 

 the Webers' experiments, the Gaskell effect. It presumably could not have 

 been the influence of Einthoven and Rademaker (1916) whose doubts were 

 expressed some two years after Keith Lucas's lectures at University College. 

 The bom fide nature of the Gaskell effect was reinstated by Samojloff in 

 1923 and recently in a most elegant fashion by Castillo and Katz (1955). 



It is useful to ponder that which must have been the conditio sine qua non 

 of the Gaskell experiment as it would appear in the light of present-day 

 experiments, for which the prototype is the observation by Fatt and Katz 

 (1953) on the crab claw. In a word, the electropositive variation observed by 

 Gaskell depended for its appearance upon a lowering of membrane potential 

 from normal resting level which in this case would have been due to demarca- 

 tion. Appreciable changes in membrane potential need not accompany vagal 

 inhibition (Trautwein et al., 1956) although they certainly do if the conditions 

 are right. 



The occurrence of a "positive variation" clearly is not an essential mani- 

 festation of inhibition (Fatt and Katz, 1953; Frank, 1959; Lloyd and Wilson, 

 1959). Further, if a positive variation is brought out by experimental means, 

 intentional or incidental, the fact of its presence does not delineate the 

 means of its causation, be it electrical or chemical. 



To return to the question of the "electrical-chemical" dichotomy, it is 

 easily seen that the chemical hypothesis in its protean form is the simpler and 

 more appealing. The endings in action liberate a substance of one or another 

 chemical species that on encountering the postsynaptic membrane acts to 

 cause excitation or inhibition. 



It is clear from the following quotation that Sherrington considered a 

 chemical, or "humoral", hypothesis. In 1925 he wrote: 



"It may further be objected to the scheme that it reduces the afferent neurone-fibre, 

 and the axones of the downstream neurones on which that acts, to somewhat the 

 character of secretory nerves. This, however, would be but in accord with recent 

 evidence in favour of a so-called humoral view of the nervous production of peripheral 

 excitation and inhibition." 



Of interest is the fact that Sherrington writing in 1931 with Eccles seems 

 to attribute the view to Samojloff and Kisseleff (1927) in the following 

 words: 



•'. . . Samojloff and Kisseleff (1927) inferred that there is a long lasting inhibitory 

 state in the reflex centre, and they suggested that it is a chemical substance of opposite 

 nature to the 'excitatory substance'." 



