414 ANNALS NEW YORK ACADEMY OF SCIENCES 



methyl to ethyl affects profoundly the physico-chemical properties 

 of a molecule. The difference between methyl and ethyl alcohol is 

 well known, and need not be discussed here. 



Nearly half a century ago, Michaelis showed that, if, in a certain dye, 

 the ethyl groups were substituted by methyl groups, no staining in- 

 side the living cell could be obtained. ^^ Since these groups are not 

 part of the molecule which has the staining properties, the loss of 

 staining power may be due to the impossibility of penetrating the cell, 

 due to the substitution performed. It appears not surprising that a 

 compound with 4 ethyl groups becomes lipoid soluble, in spite of nearly 

 complete dissociation. 



The inability to penetrate the lipoid membrane may explain why 

 ACh and prostigmine, applied externally, act only on nerve endings 

 which do not have a myelin sheath, but are inactive when applied to 

 the axon. Only in electric tissue may the power of ACh to produce 

 an action potential be demonstrated. Injection of ACh leads to 

 changes in potential of the same direction as those observed during 

 the discharge.^^ Electric tissue, however, is an accumulation of end- 

 plates which, in contrast to the axons, are not protected by myeline 

 and, therefore, do react. This may also be the explanation for the 

 famous observation of Claude Bernard on the effect of curare, since, 

 according to recent observations, the active principle of curare is a 

 quaternary ammonium salt.^^' *° 



The peculiar ability of the synapse to react to injected ACh can no 

 longer be referred to a difference in the fundamental physico-chemical 

 process underlying the propagation of the nerve impulse, but to the 

 difference in histological structure. 



Effect of Di-Isopropyl Fluorophosphate (DFP)* 



Recently, a new inhibitor of cholinesterase, di-isopropyl fluoro- 

 phosphate (DFP), became known, which can inhibit cholinesterase 

 irreversibly. Tested on the fin nerve of squid, the compound has the 

 same effect on the action potential as was observed with eserine, and 

 at about the same concentration.^^ When the nerve is kept in a solu- 

 tion of 2 mgs. of DFP per cc, the action potential is completely abol- 

 ished in about 30 minutes. When the nerve is put back into sea water, 

 the action potential comes back (figure 8) . These experiments sug- 

 gested that, for relatively short periods and at low temperature, around 

 20° C, the inactivation of cholinesterase by DFP may be partly re- 



* Most of the observations reported in this paragraph were carried out after the conference, but, 

 since the effect of fluorophosphate on the action potential and its mechanism played an important 

 role then, it appeared desirable to include these data in this paper. 



