SYNAPTIC AND EPHAPTIC TRANSMISSION 



lai 



Recently the models examined have been endowed 

 with dynamic properties (cf. 2, 9, and literature 

 cited in the papers). These current theoretical 

 formulations have had some success in accounting 

 for relations between structures of drugs and their 

 functions. They do not, as yet, consider the implica- 

 tions of the recent findings concerning specificity of 

 drug action on one or the other type of synaptic 

 membrane. Thus the addition of one carbon link to 

 an co-amino acid converts a substance which is pre- 

 dominantly an inactivator of depolarizing synapses 

 (Cs) to another (Ce) which inactivates chiefly, or 

 perhaps exclusively, the hyperpolarizing type (table 

 4; figs. 22, 23). In other relations of drugs, similar 

 abrupt transitions depending upon number of 

 carbons (the transformation occurring at about five 

 carbon.s) have also been noted (cf 14, p. 147). 



The occurrence of distinct varieties of synaptically 

 acting chcmotherapeutic agents, e.g. analgesics, 

 antipyretics, etc., bespeaks relatively sharp, though 

 not absolute, difl^erences between synaptic mem- 

 branes in differently acting regions of the central 

 nervous system. Similar distinctions, both peripheral 

 and central, derive from the relatively specific actions 

 of other drugs. Thus, whether synaptic transmission 

 is blockaded by atropine or by fZ-tubocurarine forms 

 part of the differentiation between muscarinic and 

 nicotinic cholinoceptive synapses. 



Ph ysio/og ical Im plica lio n s 



Only a few selected aspects can be discussed here 

 of the relations between the modes of action of trans- 

 mitter agents and their physiological consequences. 



a) topographic distinctions. In many cases the 

 action of a transmitter must be rather strictly lo- 

 calized. This is due to a number of factors which 

 differ in importance for diflferent transmitters and 

 synaptic sites. The small quantity of transmitter re- 

 leased by a presynaptic nerve fiber would rapidly 

 lose effectiveness upon diffu.sion and dilution in the 

 volume away from the synaptic site. It may be 

 destroyed by enzymes or fLxed in various chemical 

 combinations. Its effectiveness at other synaptic 

 sites may be small or absent. The rate at which it 

 moves from the region in which it was liberated may 

 be very slow. 



These, and other factors that may be postulated, 

 tend to restrict transmitter action to limited sites, 

 although under special experimental conditions dif- 

 fusion is easily demonstrated (cf 177). Electrical 

 ine.xcitability of .synaptic membrane and its chemical 



specificities promote restriction of transmitter action 

 which is desirable in intricate synaptic relations. The 

 specificities of different, perhaps of alternating 

 synapses in a .synaptic sequence, as suggested by 

 Feldberg (cf 157), would be one means of achieving 

 this result. In the spinal cord, interneurons and 

 motoneurons appear to have somewhat different 

 pharmacological properties (cf. 60). 



Diff'erent parts of the same neuron might also have 

 differently sensitive synaptic membranes. Thus, the 

 co-amino acids appear to be chiefly effective as 

 synapse inactivators at the superificial axodendritic 

 synapses of cortical neurons (fig. 25). In the context 

 of electrically inexcitable activity of these dendrites 

 (165) the function of dendritic electrogenesis is prob- 

 ably that of modulating somatic responsiveness, a 

 consequence which cannot be discussed here (cf. 



lOl). 



b) synaptic specificity and transmitters. Eccles 

 (cf. 60) has emphasized the implication of Dale's 

 suggestion (46) that one neuron at all its profuse 

 terminals probably generates only one type of trans- 

 mitter. This ' principle' is reasonable but is not at 

 all an obligatory condition. Furthermore, a neuron 

 secreting the same transmitter at different synaptic 

 sites may produce depolarization and be an 'ex- 

 citant' at one, or cause hyperpolarization and be an 

 'inhibitor' at another variety of synaptic membrane. 

 Likewise, the same neuron might produce at its 

 different terminals several varieties of transmitters 

 which might all have the same effect, excitatory or 

 inhibitory, or opposite actions, depending entirely 

 upon the variety of postsynaptic membrane which is 

 in synaptic relation with the transmitters. This 

 emphasizes that the nature of the transmitter can 

 determine synaptic potency and the kinetics of the 

 synaptic activity (cf 97). The type of electrogenic 

 action is determined by the postsynaptic membrane.' 



c) reciprocal interactions of neural pathways. 

 The mechanisms of dual action discussed above have 

 bearing upon the interpretation of reciprocal innerva- 

 tion. r Sherington discovered in spinal reflexes (44) 

 that the development of reflex activity in one muscle 

 is associated with concurrent inhibition of antagonis- 

 tic muscular activity. These interactions extend to 



' Interactions of some drugs evoke apparently dual actions 

 at the muscle endplatc (cf. 53). These may be cases of the situa- 

 tion commented upon earlier, in which a drug activates some 

 components and inactivates others in the same synaptic mem- 

 brane. This implies that the membrane of a single synapse is 

 not homogeneous. 



