422 ANNALS NEW YORK ACADEMY OF SCIENCES 



time, by many leading physiologists as the chief difficulty for any 

 chemical theory. It is gratifying to see that the evidence accumu- 

 lated during the last ten years for the high rate of cholinesterase activ- 

 ity appears to be so impressive that Dr. Gerard now sees in this high 

 speed one of the main difficulties. He calculates, for example, that 

 the ACh preformed, plus that synthesized, could not possibly supply 

 the ester as fast as cholinesterase can split it. 



Such an objection would only hold if the whole amount of cholin- 

 esterase present were continuously and fully active. It appears likely, 

 however, that, at any given moment, only part of the enzyme acts and 

 only for extremely brief periods. The differences found between the 

 rates of formation and removal of ACh appear, as pointed out before, 

 to be well within the expected range. 



(2) Still more puzzling to Dr. Gerard is the fact that, at the motor 

 end-plate, there is 15,000 times more cholinesterase than in the sur- 

 rounding muscle fiber, since there is no evidence for a great store or 

 synthesis of ACh at this junction. 



The difference between muscle fiber and end-plate is interesting, in 

 view of the specialized localization. It is comparable to the distribution 

 found in nerve between *surf ace and axoplasm, which is infinite. In 

 absolute amounts, the ACh which can be metabolized per impulse per 

 end-plate is 0.000002 fx,g. The formation of this amount does not re- 

 quire a particularly powerful synthesizing system nor an intensive 

 respiration. The energy required for the synthesis, even assuming a 

 high frequency, would still amount to less than one per cent of the 

 oxidative energy measured, a deviation which is far below the meas- 

 urable range. 



(3) Dr. Gerard assumes that the heat production by the ACh re- 

 leased would amount to 10 per cent of the total heat, whereas the 

 initial heat is only about 3 per cent. 



The frog's sciatic nerve is suitable for such a calculation, since here 

 more experimental data are available than in other cases. According 

 to von Muralt, 0.0006 /xg. of ACh is released per gram per impulse.*^ 

 This would amount to about 6 X 10"^ gram calories, which is 0.6 per 

 cent of the total or 20 per cent of the initial heat. 



(4) Finally, many other agents and enzymes are present in neurons, 

 like adrenaline, thiamin, adenosine triphosphate, COo, and many others. 

 Dr. Gerard asks how we can reasonably select ACh and assign to it 

 alone an essential role in conduction of the nervous impulse. Un- 

 doubtedly, there are other compounds and enzymes playing an essential 

 role in nerve activity. The ACh cycle is evidence for that. But none 



