92 D. NACHMANSOHN VOL. 4 (1950) 



acetylcholine may occur in the recovery period. In that case it would be hard to under- 

 stand how the compound produces current. Although the potential changes resemble 

 the normal discharge, there is, however, a most striking contrast in two respects: the 

 smallness of the voltage and the 1 000 fold increase of the duration. The normal discharge 

 occurs in 2 to 3 milliseconds; the voltage of a single unit is about 100 millivolts. Although 

 a quantitative evaluation is impossible since the number of units in series reached by the 

 intraarterial injection is uncertain, the discrepancy as to duration and strength is enor- 

 mous, even in presence of eserine. The method used is crude compared to the effect which 

 might be expected if the compound were released from the nerve ending. In that case it 

 would reach the opposite surface much faster, but in view of the relatively large amounts 

 injected, of which apparently at least a fraction reaches the active membrane, the 

 response is small beyond all proportion. It thus becomes difficult to conceive that 

 physiologically the substance is released from the nerve ending and, penetrating the inter- 

 cellular space, produces the end plate potential. This difficulty does not arise if it be 

 assumed that the release and the removal of the ester are intracellular events which 

 do not involve any diffusion but occur in the post-synaptic membrane and generate 

 there the flow of current. 



If locally supplied energy is necessary for the small electric currents which propagate 

 the impulse along the axon as postulated by Keith, Lucas, and Adrian, it appears 

 almost certain that such energy will be required for the generation of a potential in the 

 second unit. The flow of current reaching the post-synaptic membrane may result in 

 a release of acetylcholine which may act as a trigger in the chain of events and supplj' 

 the energy for building up the end plate potential. It is remarkable that exactly this 

 mode of action has been proposed by Lapicque'^ in 1936 — "I'etat d'excitation suscite 

 dans la sole nucleee pent y declencher une reaction auxiliaire venant fournir le supple- 

 ment de puissance requise. Tel serait le role de I'acetylcholine; c'est exactement le role 

 que joue I'amorce dans la technique des explosifs ... La production de I'acetylcholine 

 serait, dans cette conception, situee, non entre le nerf et le muscle, mais dans le muscle 

 lui-meme, auquel appartient sans conteste la sole nucleee. II s'agirait done strictement 

 parlant, non d'un intermediaire dans la transmission de I'excitation entre nerf et muscle, 

 mais d'un premier stade, formant relais dans I'excitation musculaire pour assurer sa 

 generalisation a toute la masse du myone". 



The electrogenic effect of acetylcholine injected into the electric tissue is another 

 illustration of the fact that the post-synaptic membrane is not protected against the 

 ester. It is interesting that the effect of curare on electric tissue was a controversial issue 

 for a long time. Recently, however. Auger and Fessard'^ have shown that the effect 

 of curare is regularly reproducible if the permeability factor is taken into account and 

 the drug is applied in adequate form. 



Curare, being a methylated quaternary ammonium salt, may act upon the protein 

 of the active membrane as a competitor of acetylcholine. The effect persists since the 

 compound cannot be hydrolyzed but must be removed by diffusion. If the rapid removal 

 of acetylcholine is inhibited by eserine, the result is strikingly similar to that obtained 

 with partial curarization of the end plate, as the experiments of Auger and Fessard 

 have shown. The depression and prolongation of the potential in Fig. 3 must obviously 

 be attributed to the persistence of acetylcholine and with still higher concentrations of 

 eserine a complete "curarization" will be obtained. 



As pointed out by Erlanger, conduction along the axon and transmission across 

 References p. 93I95. 



