346 DAVID R. CURTIS 



(Szentagothai, 1958, 1961) and progress in these fields may be rapid in the 

 near future. 



C. DEMONSTRATION OF THE PRESENCE OF ENZYMES 



ASSOCIATED WITH THE SYNTHESIS AND 



INACTIVATION OF THE SUBSTANCE 



Feldberg's proposals of the role of acetylcholine as a transmitter substance 

 within the central nervous system were based not only upon the distribution 

 of acetylchoHne but also upon that of chohne acetylase (cf. Feldberg, 1957). 

 If a substance be a synaptic transmitter it is reasonable to consider that 

 components responsible for its synthesis would be present both at the 

 terminations where release occurs and at the parent cell body (cf. Birks and 

 Macintosh, 1957). The problems of detecting the presence of an enzyme 

 responsible for the synthesis of a transmitter substance are the same as those 

 discussed in reference to detection of the transmitter itself, but it is possible 

 that inhibitors of such an enzyme, by blocking the synthesis of the transmitter, 

 may be useful in determining its chemical nature. 



The role of enzymes responsible for the inactivation of transmitter sub- 

 stances is not so clear. The distribution of acetylcholine esterase has been 

 determined histochemically (Koelle, 1959) and its presence near the post- 

 synaptic receptors at certain sites, together with the prolongation of the 

 acetylcholine transmitter action which follows the administration of acetyl- 

 choline esterase inhibitors, suggests that the enzyme is at least partly respon- 

 sible for the inactivation of synaptically released acetylcholine (cf. del Castillo 

 and Katz, 1956). However, other factors may also contribute to the removal 

 of transmitters (cf. Blaschko, 1956). Analysis of the ionic currents responsible 

 for the postsynaptic potentials of spinal motoneurons (Curtis and Eccles, 

 1959) indicate that the alterations in the permeabihty of the subsynaptic 

 receptor membrane which produces these currents are of brief duration. It is 

 reasonable to assume that the time course of these changes in permeability 

 are identical with the period of activity of the particular transmitter-receptor 

 complex and the further assumption that such complexes are of low stability 

 allows the conclusion that the calculated time course of the currents reflects 

 the concentration of transmitter within the synaptic cleft. On the basis of 

 this conclusion and the dimensions of synaptic clefts, it has been calculated 

 (Eccles and Jaeger, 1957) that for these central synapses, the process of 

 diffusion is adequate to account for the brief transmitter time of action 

 observed. 



The assumptions of this argument, however, are such that enzymic inactiva- 

 tion of transmitters cannot be fully excluded, and, although analogies based 

 upon events at cholinergic synapses are not necessarily applicable to central 

 synapses, the possibihty that enzymes might exist for this purpose must not 



