444 The Molecular Basis of Nerve Conduction /24 : 3 



Most esters require free energy for their formation. At equilibrium at 

 room temperature, almost all of the ester should be hydrolyzed to the 

 component acid and alcohol. Enzymes which promote this equilib- 

 rium are called esterases. In all nerve tissues, there are certain specific 

 enzymes called cholinesterases which split acetylcholine at a much faster 

 rate than do the other esterases. If acetylcholine is released, or injected, 

 its action is limited to a short period of time because the enzyme, cholin- 

 esterase, hydrolyzes the ACh in 1 or 2 msec. 



As discussed in Chapter 4, acetylcholine was discovered as a secretion 

 from the ends of the vagus nerve in the heart. Stimulation of the vagus 

 nerve slows the heart rate; this was shown to be mediated by acetyl- 

 choline. Numerous experiments have shown that acetylcholine may be 

 active in transmitting nerve impulses across synapses. This has been 

 most strongly supported by studies of neuromuscular junctions. In 

 these external cases, acetylcholine is able to produce the secondary 

 effect without the primary nerve impulses. 



Some of the evidence for the action of acetylcholine comes from a 

 study of electric eels. These animals have electric organs which are 

 effectively a series of potential generators. For a few milliseconds, they 

 can discharge as much as 6 KW with potential differences as high as 

 250 volts. The electric organs are modified motor end plates; in the 

 normal muscle, the motor end plate is stimulated by a nerve ending. 

 Indirect evidence from many lines indicates that at the active nerve 

 ending, acetylcholine is secreted which then produces the response in 

 the motor end plate. The size of the eel's electric organ makes it very 

 suitable to study this response directly, using chemical extraction pro- 

 cedures. Nachmansohn has shown that the amount of cholinesterase is 

 proportional to the emf developed. This suggests strongly that acetyl- 

 choline plays an essential role in the potential discharge of the electric 

 organ. Likewise, Nachmansohn and his co-workers have shown that 

 the formation and hydrolysis of acetylcholine in extracts can be coupled 

 to the energy-storing mechanisms of the cell, phosphocreatine and 

 adenosine-triphosphate (ATP). 



In explaining the action of acetylcholine in the conduction of spike 

 potentials along axons, it was hypothesized that ACh was released by 

 the approaching spike. The permeability of the membrane to Na + 

 and K + ions was increased by the combination of ACh with the 

 membrane. As the spike passed, the permeability was reduced because 

 of the hydrolysis of ACh by cholinesterase. Then, the ACh was re- 

 synthesized using energy from cellular metabolism. The ACh was 

 postulated to be synthesized in a bound form in order that it not act 

 on the membrane again. The resynthesis, after the spike had passed, 

 is based on very sensitive heat determinations, which revealed that 



