GERARD: NERVE METABOLISM AND FUNCTION 591 



tion of permeability; for, of course, the absence of an expected effect 

 in vivo could easily be due to a failure of the added substance to pene- 

 trate to the vulnerable region. However, the evidence marshalled 

 seems to be conclusive that esterase can be inactivated, or ACh con- 

 tent increased, without serious disturbance of function of nerve or 

 muscle. 



All agree that eserine, a tertiary amine, can enter nerve and muscle, 

 and Nachmansohn makes the point that the action potential of squid 

 nerve can be abohshed by soaking in this drug. (The fall of the ac- 

 tion potential does not show the great prolongation one might expect if 

 ACh removal were interfered with.) Yet Cantoni and Loewi have re- 

 ported"^ that a frog can be eserinized in vivo so that nerve ChE activity 

 is abolished, while nerve conduction remains undisturbed. (Con- 

 versely, intravenous ChE blocks the pupillary reflex in rats.*°) A 

 comparable result with the even more powerful, and irreversible, in- 

 hibitor, diisopropyl-fluorophosphate, has just been presented by Oilman 

 and by Bodansky. Both in vivo and in vitro, though with some 

 anomalies in behavior, this agent has been shown to inactivate entirely 

 ChE while leaving nerve conduction and action potentials intact. Al- 

 though detailed criticisms have been made, especially by Talbot, the 

 major fact remains, as in the eserine experiments, that conduction with- 

 out esterase is possible.* Again, veratrm can inhibit ChE,^^ yet it does 

 not^- influence muscle or the neuromyal junction, including its sensitiv- 

 ity to added ACh, except for a late and independent negativity. 



The inability of ACh, added in large concentration to the surround- 

 ing medium, to depolarize nerve or otherwise to disturb conduction, has 

 been reemphasized by the new experiments of Lorente de No and of 

 Bronk. Nachmansohn has urged that ACh, a quarternary ion, cannot 

 penetrate the lipoid membrane of nerve fibers, except at their naked 

 terminals, thus accounting for these negative results. Yet ACh does 

 leave nerve trunks on stimulation and should, similarly, be able to 

 enter under combined anoxia and stimulation. Further, both Bronk 

 and Atcheson have presented clear evidence that tetraethylammonium 



* The results of Gilman and the Edgewood workers have since been challenged by Nachman- 

 sohn and his colleagues. Both groups reported work at the April meeting of the Federation, and 

 their full papers have since appeared (J. Neurophysiol. June). Work done in the interval in my 

 laboratory fully supports the conclusions of the Edgewood group. 



Frog sciatics were immersed in peanut oil, with or without DFP, resting on stimulating and 

 lead-off electrodes. Action potentials fail in a few minutes or remain normal for hours, depending 

 on the drug concentration. Conduction, when lost, is not restored in fresh oil. A nerve exposed 

 for an hour to a non-depressing concentration of DFP, washed, ground, and assayed for cholin- 

 esterase by its rate of destruction of added acetylcholine (tested on the frog's rectus), shows no 

 cholinesterase activity. A companion nerve continues to conduct well, while remaining in the same 

 DFP solution. Further, when a washed, poisoned nerve is ground together with an untreated one, 

 the homogenate assays at the average cholinesterase activity of the two nerves taken separately. 

 The DFP inactivation of cholinesterase occurs, therefore, prior to the grinding. Clearly, conduc- 

 tion is possible in nerve lacking cholinesterase. 



