NACHMANSOHN: CHEMICAL MECHANISM IN NERVES 403 



ACh metabolism may be due essentially to the effect of the ester on the 

 resistance of the boundary or, which is equivalent, on its permeability. 



Thus, we arrive at the following picture of the role which ACh may 

 have in the mechanism of nerve activity : According to the membrane 

 theory which is most widely accepted among physiologists, the nerve is 

 surrounded by a polarized membrane. The polarized state of the 

 membrane is due to a selective permeability to potassium ions which 

 are many times more concentrated inside the axon than outside. Dur- 

 ing the passage of the impulse, the permeability of the membrane to 

 negative ions is increased, and a depolarization occurs. The rapid ap- 

 pearance and removal of ACh may be an event essential for this change 

 in permeability. The depolarized point becomes negative to the adja- 

 cent region, and flow of current results. This flow of current stimu- 

 lates the next following point. There again, ACh is released, and the 

 whole process repeated. The impulse is thus propagated along the 

 axon. Cholinesterase destroys the active ester very rapidly, and the 

 state of polarization may hereby be restored. 



At the nerve ending, other factors, like increased surface and de- 

 creased resistance leading to a greater flow of current, may act in ad- 

 dition. But the process is fundamentally identical, the transmitting 

 agent being the flow of current. Whereas, in earlier theories, ACh 

 was considered as a "neurohumoral" or "synaptic" transmitter, i.e., a 

 substance released from the nerve ending and acting directly on a sec- 

 ond neuron, in the new concept it is assumed that the transmitting 

 agent is always the electric current, the action potential, but the re- 

 lease of ACh is necessary for generating the current. 



The picture is consistent with the idea of the propagation of the 

 nerve impulse as developed by Keith Lucas and Adrian. It becomes 

 unnecessary to assume that the transmission along the axon differs fun- 

 damentally from that across the synapse. The assumption of a special 

 mechanism at the synapse, different from that in the axon, as empha- 

 sized before, was the chief difficulty which had to be overcome to 

 reconcile the original theory with the conclusions of the electrophysi- 

 ologists. This appeared necessary for any satisfactory answer to the 

 problem. If it is true that physical methods alone are unable to ex- 

 plain the mechanism in a living cell, it is equally true that conclusions 

 based on chemical methods should not be in contradiction to those ob- 

 tained with physical methods, in view of the much higher sensitivity 

 of the latter. 



The picture of the transmission of the nerve impulse across the syn- 

 apse is, however, far from being complete, if only the flow of current 



