588 ANNALS NEW YORK ACADEMY OF SCIENCES 



caping from the ganglion, per impulse, is thus only about one-fiftieth of 

 the amount that the ChE present could split in one millisecond. If ChA 

 activity is taken to be one-thousandth that of ChE, the ACh synthesized 

 in 60 ms. (the interval between impulses) could equal that released or 

 exceed it two- or three-fold. This, incidentally, leaves no place for the 

 often-assumed existence of a much greater ACh turnover within active 

 units than is reflected in the amount escaping from them. 



Isolated frog nerve, according to von Muralt,*^' actually increases its 

 ACh content on tetanization, from lO"*' at rest to 1.5 X 10"*^ while ac- 

 tive, and the ACh increase per impulse calculates to 6 X 10"^ from von 

 Muralt's figures, to 10~" from Lissak's.^^ (In the latter experiments, 

 only the ACh diffusing from the cut ends of a stimulated nerve was 

 measured.) For cat gastrocnemius, assuming a weight of 20 grams, 

 the ACh released by a single maximal twitch evoked by the nerve is 

 6 X 10"^^ mM/gm.^* Nerve can, of course, conduct several hundred 

 impulses per second for long periods, but we might conservatively cal- 

 culate with 50 per second, or 20 milliseconds total time available per 

 impulse. Frog nerve ChE could split in this period 3 X 10"'^ mM/gm. 

 of ACh: five times the amount von Muralt finds liberated and 30,000 

 times Lissak's figure. If, again, ChA is only one-thousandth as active, 

 it could easily supply ACh at the rate demanded by Lissak but would 

 fall short of von Muralt's figure by 100-fold. On the basis of such 

 an analysis, a nerve should be able to conduct an impulse only once 

 in two seconds. Von Muralt's value, incidentally, is far more in ac- 

 cord with that for the ganglion, both in absolute amount and in rela- 

 tion to ChE activity, and it is also more probably correct on method- 

 ological grounds. But it cannot be right if the assumed ChA activity 

 is remotely correct. 



Perhaps, then, all these discrepancies result from falsely low ChA 

 values. This enzyme system might easily have been seriously injured 

 during tissue extraction and, thus, be far more active in vivo. Let us 

 make this assumption, and allow a ChA activity sufficient to equal ChE 

 activity or, giving ACh the most favorable conditions, an activity 

 sufficient only to cover the ACh actually released on stimulation. Note, 

 however, that even this excludes any greater ACh formation and sub- 

 sequent destruction, within the cell or outside it, beyond the measured 

 formation. If this greater turnover is allowed, by assuming ChA 

 activity to equal ChE, the following relationships reveal still more in- 

 tolerable discrepancies. 



The formation of one millimole of ACh requires, we have agreed, 

 some 2 calories. The sympathetic ganglion, releasing ACh on stimula- 



