ECCLES: ELECTRICAL THEORIES OF TRANSMISSION 447 



pulses was used as the criterion of end-plate excitability. Yet, if the 

 end-plate region reacts by local responses, rather than by propagating 

 impulses (part 4, C), it seems probable that this investigation tested 

 the excitability, not of the end-plate {i.e., of the post-synaptic mem- 

 brane), but of the membrane adjacent thereto, confirming the previ- 

 ously observed absence, there, of curare action. '^^' '^- '* Thus, it pro- 

 vides no evidence for, or against, a specific depression of electrical ex- 

 citability of the post-synaptic membrane. Alternatively, if curarine 

 blocks solely by its known depressant action on the local potentials set 

 up by acetylcholine,"' ^^' ^* then, in very deep curarization, the re- 

 sidual catelectrotonic effects produced by the cathodal focus, i.e., by 

 electrical transmission, should be observable, uncomplicated by chem- 

 ical transmission. This inference is particularly pertinent in the case 

 of sympathetic ganglia, where the synaptic potential is virtually abol- 

 ished by deep curarization, and yet other evidence suggests that acetyl- 

 choline transmission plays but a minor role (part 2, ii) .^^ 



B. Action of Anti-Cholinesterases on Synaptic Transmission with 

 Skeletal Muscle and Sympathetic Ganglia 



Anti-cholinesterases (eserine, prostigmine) delay the summit of the 

 curarized end-plate potential and slow its decline,^^- ^■*' ^^ effects which, 

 undoubtedly, are attributable to a prolongation of the active depolar- 

 izing agent. With rapid, repetitive stimulation, a still greater effect is 

 observed, the end-plate potential persisting for several seconds, both in 

 curarized and normal muscle."- ^^ With sympathetic ganglia (normal 

 or curarized), anti-cholinesterases also cause a prolonged synaptic po- 

 tential to appear, after rapid, repetitive stimulation, but this prolonged 

 potential is sharply distinguishable as a special addition to the other- 

 wise unaltered synaptic potential.-^ Presumably, both with ganglia 

 and muscle, the prolonged potential is due to acetylcholine liberated by 

 pre-synaptic impulses.* With ganglia, it has been argued that, since the 

 initial, brief transmitter action, setting up the synaptic potential, is un- 

 affected by anti-cholinesterases, it is not due to acetylcholine.^^ Simi- 

 larly, with muscle, the eserinized (or prostigminized) end-plate poten- 

 tial appears to be the partly fused compound of a brief, initial phase, 

 but little, if at all, lengthened by the anti-cholinesterase and the pro- 

 longed phase (certainly due to acetylcholine) .f Thus, the electrical 

 hypothesis would attribute the effect of anti-cholinesterases to an in- 

 tensification and great prolongation of the normally small transmitter 

 action of acetylcholine. Incidentally, it may be noted that such an 



• However, cf. ITachmansolin, D."* 



t Eccles, J. C, B. Xatz, 8c S. W. Kuffler.^" Figure 5. 



