24 : 3/ The Molecular Basis of Nerve Conduction 



445 



heat was generated after, not during, the spike. The interrelated 

 biochemical processes are shown in Figure 4. 



There are a number of weaknesses of the ACh hypothesis. Most 



V 0-r^ 



O-r 



Elementary Process 



-T- 



Glucose 



.© 



II 



r^O-i-^, 



ffi^ 



Choline Acetate 



2 ATP 



+ o 2 



Anaerobic 



30 ATP 



CoA ♦ Acetate 



Choline} ^ Acetyl -CoA 



Acetylase J J 



ATP 

 Pool 



^ 



Phosphocreatine 



Figure 4. Sequence of energy transformations associated with 

 conduction and integration of the acetylcholine system into the 

 metabolic pathways of the nerve cell. The elementary process 

 of conduction may be tentatively pictured as follows: 



(1) In resting condition acetylcholine (O-w ) is bound, pre- 

 sumably to a storage protein (S). The membrane is polarized. 



(2) ACh is released by current flow (possibly hydrogen ion 

 movements) or any other excitatory agent. The free ester 

 combines with the receptor (R), presumably a protein. 



(3) The receptor changes its configuration (dotted line). 

 This process increases the Na ion permeability and permits its 

 rapid influx. This is the trigger action by which the potential 

 primary source of emf, the ionic concentration gradient, 

 becomes effective and by which the action current is generated. 



(4) The ester-receptor complex is in dynamic equilibrium 

 with the free ester and the receptor; the free ester is open to 

 attack by acetylcholinesterase (E). 



(5) The hydrolysis of the ester permits the receptor to return 

 to its original shape. The permeability decreases, and the 

 membrane is again in its original polarized condition. After 

 D. Nachmansohn and I. B. Wilson, in Currents in Biochemical 

 Research — 1956, D. E. Green, ed. (New York: Interscience 

 Publishers, Inc., 1956). 



glaring is its failure to provide a possibility for all the rate constants 

 shown necessary in the next subsection. In addition, if a compound 

 blocking cholinesterase is applied to a nerve, the action potential is 



