NACHMANSOHN: CHEMICAL MECHANISM IN NERVES 411 



gram per cent solution of ACh for many hours, and did not find any 

 effect on conductivity. He considers his failure to obtain an effect on 

 the axon by ACh as proof against the new concept of the role of ACh 

 in the mechanism of nerve activity. ACh is a quaternary ammonium 

 salt. Such compounds are completely ionized and usually lipoid 

 insoluble. Generally, they do not penetrate the lipoid membrane. 

 Therefore, these compounds can be expected to have no effect on the 

 axon, since axons are always surrounded by a lipoid membrane, even 

 though it may be rather thin. 



1 



i 





V 



A 



'iT 



Figure 5. Effect of eserine on single fiber action potential (giant axon of squid). 



Left: eyerine 0.002M, records (from top to bottom) at 0', 10', 25' (conduction abolished), 35'; 

 sea water at 26'. Conduction distance less for last record, too short to demonstrate latency effect. 



Right: eserine O.OIM, records at 0', 15', fiber then rinsed, and axoplasm analyzed chemically. 

 Upper time scale applies to this experiment, lower to column at left, both 1000 c.p.s. 



The problem has been approached in a different way: If ACh is the 

 depolarizing agent and if the function of cholinesterase is to remove 

 the active ester, so that polarization again becomes possible after the 

 passage of the impulse, then inhibition of the enzyme should alter, and, 

 in sufficiently high concentration, abolish, the nerve action potential. ^"^ 



Eserine is known to be a strong inhibitor of cholinesterase. This 

 compound is a tertiary amine and may, therefore, if undissociated, 

 penetrate the lipoid membrane. Experiments carried out on the giant 



