NACHMANSOHN: CHEMICAL MECHANISM IN NERVES 423 



of these compounds shows the typical features of the ACh system, like 

 the high speed, the exclusive localization in the surface, the parallelism 

 with voltage, etc. These unique features of the ACh system make it 

 possible to associate the ester more closely with the action potential !* 

 than all other agents so far known. 



SUMMARY AND CONCLUSION 



In view of the complex nature of biological mechanisms, one or two 

 facts, however well established and suggestive, would not be sufficient 

 for any theory. However, if a great number of facts point in the same 

 direction, then they support each other and potentiate the value of each 

 of them. The essential facts established may be summarized: (1) 

 The high concentration of cholinesterase in nerve tissue makes possible 

 the removal of ACh at a speed comparable to that of the electric mani- 

 festations. (2) Cholinesterase is localized everywhere at the neuronal 

 surface where the bioelectrical phenomena occur. The exclusive local- 

 ization in the surface contrasts strikingly with the localization of other 

 enzymes. (3) Cholinesterase in nervous tissue (and in muscle) is 

 distinctly different from all other tissue esterases occurring in the body. 

 The enzyme, present in all types of nerves throughout the entire animal 

 kingdom, shows similar properties. (4) A direct proportionality be- 

 tween voltage and cholinesterase activity has been established in the 

 electric organ of Electrophorus electricus. (5) The primary energy 

 source of recovery after the passage of the impulse, namely, the energy- 

 rich phosphate bonds of adenosine triphosphate, is used for ACh syn- 

 thesis. (6) The formation of ACh by choline acetylase occurs at a 

 high rate in the peripheral fibers, as well as in the brain. The enzyme 

 has, so far, been found exclusively in nerve tissue. (7) Anticholin- 

 esterases alter, and, in high concentrations, abolish, the nerve action 

 potential. The abolition of the action potential is reversible, if the 

 inhibition of cholinesterase is reversible; irreversible inhibition of 

 cholinesterase abolishes the nerve action potential irreversibly. 



These facts considered altogether make it highly probable that the 

 release and removal of ACh is an intracellular event, directly associated 

 with the nerve action potential. 



The precise function of the ester is still a matter of interpretation. 

 On the basis of the physical and chemical data available, one possible 

 interpretation appears to be that the ester plays an essential role in 

 the breakdown of the membrane resistance, occurring during the pass- 

 age of the impulse. New facts may change the situation. A number 



