HARRY CRUNUFKST I29 



would be averaged over the entire membrane by electrotonic spread and would 

 be small if only a few 'units' were active. Thus, step-wise elect rogenesis may 

 develop larger or smaller graded responses, or a spike, depending upon this 

 number and upon the temporal relations of the triggering of the population. 

 Recent work (3a) supports these conclusions. Whereas an appropriately poi- 

 soned eel electroplaque responds gradedly to punctate electrical stimuli, only 

 a response which is identical with the spike results from simultaneous excitation 

 of the entire membrane. As will be described below, (p. 142) the graded response 

 of postsynaptic membrane is also probably caused by discontinuous electro- 

 genie activity. 



Sodium inactivation and potassium conductance probably follow different 

 kinetics in the eel electroplaque than in squid axons (4) and such a difference in 

 crayfish stretch receptor cells could account for the rapidly or slowly adapting 

 types (68, 69, 133, 188). Other data also indicate that sodium inactivation is 

 conditioned by additional factors as well as by membrane depolarization. Ca"'^" 

 deficiency or excess and anesthetics modify sodium inactivation without sig- 

 nificantly changing the resting potential (184). 



c) Mediation of Electrical Excitability. The chemical intermediates of 

 electrical excitability, if any are needed for this process, are unknown. The 

 charges of the local circuit current might themselves cause a breakdown of 

 some complex elements of the membrane, and the resulting change in fixed 

 membrane charges (presumably of long-chain lipoproteins) then might initiate 

 ionic flows. Acetylcholine, which plays an important role in synaptic trans- 

 mission (56, 60, 141), is also released intracellularly during stimulation of a 

 nerve (13, 7,7,). This fact has been incorporated into a scheme (150) which 

 considers that acetylcholine is released by the action of the local circuit, com- 

 bines with membrane components ('receptors') to produce the ionic valving of 

 permeability change, and on its destruction by an esterase the response ends. 

 This theory rests on circumstantial evidence (cf. 94) chiefly deriving from 

 correlations of the inactivation of the propagated activity and of cholinesterase 

 by various poisons (28). 



The strongest of this evidence (cf. 95, p. 30) was the finding that pretreat- 

 ment of nerves with eserine prevented their irreversible inactivation by DFP. 

 However, dysfunctions of this enzyme can no longer be considered a primary 

 cause of inactivation of electrically excitable membrane. This is not afifected 

 directly (3) by a strong anticholinesterase (Prostigmine), by acetylcholine itself 

 or by its analogs (succinylcholine, carbamylcholine or DMEA), but secondarily 

 by their depolarization of the cell through action on the postsynaptic mem- 

 brane (fig. 4). Other strong anticholinesterases (eserine, DFP) which inactivate 

 the latter, as do the curares (6, 41), do not destroy the electrogenic capacity of 

 the electrically excitable component, but change it from explosive to graded 

 responsiveness. 



The latter finding probably explains the apparent inactivation of axons by 



