NACHMANSOHN: CHEMICAL MECHANISM IN NERVES 421 



thesis is a slow recovery process. It is, therefore, not difficult to as- 

 sume that the period required for the formation is longer than that for 

 the hydrolysis of the same amount, according to the kind of nerve, 

 its condition, temperature, and so on. 



In the initial phase of nerve stimulation, the preformed ACh would 

 act as a reserve and would make conductivity independent of the rate 

 of ACh formation for a considerable length of time. Even the few 

 /ig. of ACh found per gram of nerve would be sufficient to make possible 

 the passage of several thousand impulses. The actual amount of pre- 

 formed ACh in the living cell may be higher than that found experi- 

 mentally, since it is possible that, during the destruction of the cell, a 

 process necessary for the determination, a considerable part of the 

 preformed ester is destroyed. A nerve should, therefore, be able to 

 respond to stimulation for a considerable length of time, independent 

 of the rate of ACh formation. Only in cases of prolonged stimulation 

 should the rate of formation become the limiting factor. If all pre- 

 formed ACh has been exhausted, and stimuli are applied to mammalian 

 nerve every five milliseconds, then the amount synthesized in the 

 intervals between stimuli should be sufficient for producing the 

 necessary alterations in the membrane when released by a stimulus, and 

 should be equivalent to the amount actually destroyed, during the 

 passage of the impulse, by cholinesterase. Since, in mammalian nerve, 

 the duration of the spike is only 0.5 millisecond and the cholinesterase 

 may have acted only during part of this period, e.g., 0.1 or 0.2 milli- 

 seconds, a difference of 25 to 50 times between the actual rate of cholin- 

 esterase and that of choline acetylase activity would keep the nerve 

 going indefinitely, if this were the only factor involved. 



In summary, considering the difference between the rates of cholin- 

 esterase and choline acetylase, we have to keep in mind: (1) that there 

 is a fundamental difference of function; (2) that the cholinesterase 

 activity determined is probably the maximum possible, whereas the 

 choline acetylase activity found in vitro is almost certainly below the 

 optimal rate in vivo; (3) that the excess of cholinesterase may be 

 greater than that of choline acetylase. In view of this situation, the 

 difference between the rates found does not offer any difficulty and, 

 in fact, appears close to that which one would expect of these two 

 enzymes so different in function and properties. 



As to the criticism of Dr. Gerard, who resolutely rejects the con- 

 cept presented, some of his main objections may be discussed briefly. 

 (1) The high speed required for any chemical reaction associated with 

 the transmission of the nerve impulse has been considereii-ler-^^P^S 



