448 ANNALS NEW YORK ACADEMY OF SCIENCES 



acetylcholine effect would account well for the latter part of the rela- 

 tively long transmitter action observed at normal neuro-muscular junc- 

 tions (5 msec, frog;^^ 6 msec, cat^^.) A similar investigation of the 

 synaptic potentials of motoneurones fails to reveal any such effect of 

 anti-cholinesterases. Hence, it would appear that acetylcholine plays a 

 negligible role at such synapses. These experiments indicate that the 

 synapses of nerve-muscle, sympathetic ganglia, and the spinal cord 

 form a series of decreasing significance for acetylcholine transmission. 

 There has been no reference to other effects of anti-cholinesterases on 

 synaptic transmission, e.g., after-discharge,*'' "' -^' ^^ local contrac- 

 ture,^' ^•^' ^^ lengthening of refractory period, ^^' ^^ or catelectrotonic 

 block,^' ^^' ^^' 2^ because these are all secondarily produced by the pro- 

 longed and intensified synaptic potential. 



C. Repetitive Synaptic Transmission 

 There is but little diminution of the synaptic potential set up in 

 curarized mammalian muscle^'' or anesthetized motoneurones^'^ by a 

 second pre-synaptic volley, at the shortest intervals after the first. 

 With curarized ganglia, the second potential is usually a little in- 

 creased.-' The great increase with the frog's end-plate potential^*'' ^*' 

 ^■^' '^ raises a further, as yet insoluble, problem. Since local responses 

 are followed by refractory periods,*-' ^" assumption C of the hypothesis 

 (part 4) would predict a considerable diminution of a second synaptic 

 potential, at short intervals. However, it must be remembered that 

 the above observations relate to synaptic potentials diminished suffi- 

 ciently for synaptic blockage, and that small local responses set up 

 much less refractoriness than large responses."' '" A large diminution 

 of synaptic potential is observed, when synaptic transmission is not 

 blocked,-**' -"' ^'^ and has, hitherto, been attributed to the refractoriness 

 of the post-synaptic cell. Nevertheless, it may be, in part, due to re- 

 fractoriness, following the postulated large local responses of the spe- 

 cialized post-synaptic membrane (part 4, C). This latter explanation 

 is supported by the observation that the diminution is lessened by sub- 

 paralytic curarization.* 



8. TESTING THE HYPOTHESIS 



It has been shown that the hypothesis gives a satisfactory explana- 

 tion of all experiments investigating the temporal factors in synaptic 

 transmission. It is otherwise with the intensity factors. Before the 

 hypothesis can be regarded as well established, it has to be shown that 



* Bccles, J. C, & S. W. Xaffler'»: 505. 



