GERARD: NERVE METABOLISM AND FUNCTION 587 



The total ACh present in whole brain is, keeping to millimoles per 

 gram fresh tissue, about 2 X 10"^ for mammals and twice as much for 

 the frog. White matter contains ten-fold less, but the value for mam- 

 malian mixed nerve is close to 3 X 10'^. Dorsal roots contain, at most, 

 one-twentieth of this amount; frog nerve,"' even less, 10~®. All the 

 ACh in mammalian brain could, therefore, be destroyed by ChE in 

 about 50 milliseconds, and would require a minute to be synthesized 

 by ChA. For mammalian nerve, the stored ACh could last less than 

 two seconds and would require over three minutes to replace ; for frog 

 nerve, the ACh could last about 65 milliseconds, and for mammalian 

 white matter (not to mention dorsal root), a third of a second. Yet 

 nerve, including roots and central tracts, can maintain activity for 

 hours, conducting hundreds of impulses per second ; and activity of the 

 central grey can also long outlast the possible time limits. Clearly, 

 then, neither ACh storage nor synthesis, nor both combined, could 

 possibly (unless an entirely different order of ChA exists in vivo than 

 has been found in extracts) supply this substrate as fast as ChE can 

 split it. 



Of course, an enzyme is not always kept saturated with substrate. 

 However, this at once undermines the many arguments that have been 

 made, from high ChE concentration, for the possibility of rapid rise and 

 fall of ACh concentration; it also throws into question the significance 

 of high local ChE concentrations. The striking finding, for example, 

 that ChE is 15,000 times or more as concentrated in the end-plate re- 

 gion as in the adjoining nerve or muscle, adds confusion rather than 

 insight. The end-plate potential falls much less rapidly than that of 

 nerve or muscle, and there is no evidence of a great store or synthesis 

 of ACh there. How, then, can the tremendous ChE activity be recon- 

 ciled with any current theories relating ACh to neural functioning? 

 When a 2000 horse-power engine is found in a half-ton truck, one must 

 suspect it is there for some other reason than to supply ordinary motive 

 power. 



Let us agree, however, that ChE is not kept fully saturated, and con- 

 tinue with these calculations. The cat cervical sympathetic ganglion 

 releases ACh to perfusing fluid, on preganglionic stimulation. Again 

 in millimoles per gram, the ACh content of the ganglion, before or 

 after several hours' tetanus, is about 10"^, although five times this 

 amount has been released during the activity period. The rate of re- 

 lease falls with continued activity, but holds up better when some blood 

 is present. A maximum of 10"* is liberated in five minutes' tetanus at 

 17 per second or, per impulse, about 2 X 10~^ (cf. "• ^^). The ACh es- 



