GERARD: NERVE METABOLISM AND FUNCTION 585 



duce; but, at present, relating specific actions to specific effects would 

 be mainly guesswork. It will suffice to recall that K^ increase leads 

 to such effects as: a rise, passing into a severe fall, for the irritability, 

 membrane potential, and electrotonic spread in nerve fibers, and, per- 

 haps, for their oxygen consumption, as Brink mentioned; and a fall, 

 from the start, for the spike (only slight), after-potential, conduction 

 velocity, and recovery rate. Similar changes have been observed 

 less fully in muscle and in the central nervous system: moderately in- 

 creased K+, for example,^^' 2'' '^^ increases the fast electrical activity 

 of cat or frog brain and prolongs the after-discharge on stimulation of 

 deep cerebellar nuclei (see also ^^) . There are, thus, ample roads from 

 current flow, through altered ion concentration and chemical reaction 

 rates, to physiological responses. The problem is not to find connec- 

 tions, but rather to identify the few important actualities among the 

 many conceivable possibilities. This brings us back to acetylcholine. 



THE ROLE OF THE ACETYLCHOLINE SYSTEM 



That ACh is formed and destroyed as an integral part of impulse 

 propagation in nerve fibers, has been suggested by several workers"^' '^^ 

 and strongly supported by Nachmansohn.*'" He has summarized his 

 arguments here : ACh is present in nerve and is released on stimulation 

 (though its leaving the cell is accidental) ; cholinesterase (ChE) in 

 nerve is highly active and specific, and choline acetylase (ChA) is 

 also rich in nerve; a close parallelism exists, in the electric organ, be- 

 tween potential and ChE activity; energy relations, in electric organ 

 and nerve, are satisfactory for ACh synthesis via CrP, etc.; various 

 drug actions, though always in danger of misinterpretation, especially 

 where penetration through a membrane is involved, do support the im- 

 portance of ACh in conduction. Just what the role of ACh is, seems 

 less defined. Earlier, Nachmansohn supposed that the stimulus liber- 

 ated ACh directly and that this caused the membrane depolarization. 

 Now, recognizing that the stimulus itself must lead to depolarization, 

 he suggests that ACh is responsible for the loss of resistance in the 

 membrane — certainly, a step for which a chemical mechanism would 

 be welcome. Beutner and Barnes have also emphasized a function 

 for ACh, both in producing the action potential and in lowering mem- 

 brane resistance. 



Quantitative Relations 



The calculations (Nachmansohn), that the ChE at a motor end- 

 plate is powerful enough to split a complete layer of ACh in a milli- 



