NERVE ACTIVITY 



ability and thus the generation of the electric potential. Al- 

 though the acetylcholine receptor has not yet been isolated, the 

 most likely assumption appears to be that it is a protein. Some 

 data to be discussed later suggest that by its reaction with acetyl- 

 choline the configuration of the protein is changed. 



The complex between acetylcholine and its receptor is in 

 dynamic equilibrium with the free ester and the receptor. The 

 free ester is susceptible to attack by the esterase and its hydrolysis 

 permits the receptor to return to its resting condition. The bar- 

 rier for the rapid ion movements is thus reestablished. This ac- 

 tion of the enzyme leads to immediate recovery and ends the 

 cycle of the elementary process. The rapidity of the restoration 

 process is made possible by the high speed of the enzymatic 

 hydrolysis, which may occur in microseconds. Thus the nerve 

 may respond to the next stimulus within a few milliseconds. 

 The further recovery leads to the resynthesis of acetylcholine in 

 its bound form and to the restoration of the concentration gradi- 

 ents. 



A sharp distinction must be made between the activity and 

 recovery phases. The flux of sodium and of potassium dur- 

 ing activity is in the direction of the concentration gradients. 

 The suddenly increased rate of flow for the extremely short period 

 of time requires very little energy to effect the transient change of 

 permeability. The change in permeability is only a trigger 

 process making the potential energy effective. This view is sup- 

 ported by the extremely small amount of heat released during 

 nerve activity, which is, at most, of the order of magnitude of 

 10~^^ of one small calorie per square centimeter per impulse. 

 Fundamentally different is the situation in respect to the ion 

 movements during recovery. The restoration of the original 

 steady state requires extrusion of sodium and uptake of potassium 

 against the concentration gradient. These latter processes re- 

 quire a relatively large amount of energy in excess of that neces- 

 sary for maintaining the resting condition. Most of the heat pro- 

 duced during nerve activity is developed after the electrical 

 changes and is presumably associated with the restoration of the 



635 



