SYNAPTIC AND EPHAPTIC TRANSMISSION 



163 



where appropriate data are available (of. 97) the 

 neurally evoked response arises after an appreciable 

 irreducible latency (fig. 6), or synaptic delay (44; 

 cf. 140). 



Between the arrival of the presynaptic impulse and 

 the onset of the p.s.p. of cat motoneurons there is a 

 latency of about 0.3 to 0.4 msec. (59, p. 130). In the 

 eel electroplaque the latency attains i to 2.5 msec. 

 (4). This delay is not conducive to, nor consistent with, 

 electrical excitation of synaptic membrane by the 

 action current of the presynaptic impulse (97) as was 

 pointed out by du Bois-Revmond (55) and Bernstein 

 (20). 



Presumably, synaptic latency is compounded from 

 the durations required: (T) for release of transmitter 

 from the presynaptic terminals; («) for its transit 

 across a synaptic space of about 100 A (52, 54, 152, 

 153' '74' 553)' ^"^^ ("') fo'" development of the 

 electrogenic reactions when the transmitter acts 

 upon the postsynaptic membrane. The details of 

 none of these components are as yet known. 



e) electrotonic effects of presynaptic impulse 

 UPON postsynaptic region. Intracellular recording 

 revealed (cf. 59, 60) that the presynaptic spike not 

 only arrived too early, but also that its electrotonic 

 efTect was too little to cause electrical excitation of the 

 postsynaptic membrane. Indirect stimulation of the 

 eel electroplaque (fig. 6C, D) excites the terminal fibers 

 innervating the cell membrane. Their spikes must 

 have occurred with vanishingly small latency upon 

 strong stimulation (Z)). However, no trace of elec- 

 trotonic effects in the electroplaque was found. The 

 presynaptic impulses could not be observed even at 

 high sensitivity of recording (fig. 3). In other prepara- 

 tions small, brief as well as early electrotonic pick up 

 of the presynaptic spikes is observed (cf. figs. 19, 

 2 J A). The magnitudes, i or 2 mv, are insignificant for 

 electrical excitation which requires critical depolari- 

 zations of some 10 to 40 mv. 



Among the possibilities for accounting for the small- 

 ne.ss of electrotonic effects across synapses are the 

 following. 



/) Theresistanceof one or both cell membranes may 

 be very high. In most types of synapses the presynap- 

 tic terminals making contact with postsynaptic 

 membrane are very small and this alone would de- 

 crease the electrotonic effects. However, the contact 

 between the pre- and postfibers in the .squid giant 

 axon synapse are broad, yet the electrotonic post- 

 junctional potential is small (fig. 19). Likewise, in the 

 eel electroplaque where the innervation is diffused 



widely over the cell membrane electrotonic effects are 

 small. 



2) The bulk of the synaptic current may be shunted 

 by the subsynaptic space. 



3) If the nerve terminals were themselves elec- 

 trically inexcitable neurosecretory regions the spike 

 would not invade the nerve proximate to the synapse. 

 The extrinsic current in the synaptic region would 

 thus be already attenuated by electrotonic losses. 



f) CHEMICAL SENSITIVITY OF SYNAPTIC MEMBRANE. 



Many varieties of drugs exert effects upon synapses, 

 but they either do not affect electrically excitable 

 membrane or do so only when applied in high con- 

 centrations and for long times (6, 96). The high 

 sensitivity of synaptic membrane to chemicals is prob- 

 ably also a con.sequence of its chemical excitability. 

 Thus, many drugs cause synaptic electrogenesis, 

 thereby mimicking the effects of the natural trans- 

 mitter agents. The.se substances are known as ' de- 

 polarizing drugs' but are more properly designated 

 as 'synapse activators' (95, 96) for their action is 

 merely that of excitants. The type of synaptic electro- 

 genesis is determined by the nature of the synapse 

 itself For example, acetylcholine and its mimetics 

 cause depolarization when applied to muscle end- 

 plates or sympathetic ganglia, but when applied to 

 the cardiac pacemaker synapses which are hyper- 

 polarized by vagal stimuli the drugs also cause hyper- 

 polarization (49, 1 20). A second group of substances, 

 the' synapse inactivators', hinder or prevent excitation 

 of the membrane bv the activator drugs. These are 

 also called ' nondepolarizing competitive inhibitors' 



(155)- 



Both types of substances may cause block of trans- 

 mission. Depolarizing excitatory p.s.p.'s are dimin- 

 ished in amplitude or prevented by the inactivating 

 drugs. The decrease of the p.s.p. below the critical 

 level for discharging spikes is the mechanism of the 

 synaptic blockading action of these drugs. Curare or 

 </-tubocurarine act in this way (fig. 15). A general 

 feature of blockade by inactivating drugs is that the 

 electrically excitaijle membrane is affected little or 

 not at all. Thus, the postjunctional cell can remain 

 directly excitable. 



Synapse-activating drugs induce transmissional 

 blockade by an entirely different mechanism which is 

 referrable to the fundamentally different excitabilities 

 of electrogenic membrane. Acting on the synaptic 

 membrane, the drugs evoke depolarization of the 

 excitatory synapses. This electrogenesis, sustained in 



