138 PHYSIOLOGICAL TRIGGERS 



when it is treated with acetylcholine, whereas were the drug an electrogenic 

 agent, a fall might be expected. 



e) Release of Transmitters. The process by which a transmitter is released 

 at the synapse is as yet only partially known, and this chiefly from work on the 

 muscle end-plate by Katz and his collaborators (cf. 36, 38, 39). 'Miniature' 

 e.p.p.'s which probably represent spontaneous releases of unit small quantities 

 of transmitter (76) occur more frequently when the pre-junctional nerve fiber 

 is electrotonically polarized (36), suggesting that the neural impulse propagating 

 into these terminals might be an adequate stimulus for release of the trans- 

 mitter. However, miniature responses still occur when the pre- and post-units 

 have become electrically irresponsive in preparations depolarized by K2SO4 

 and deprived of sodium and chloride (39). Ca"*"*" increases the quantity of 

 transmitter released, while Mg"*^ has the opposite effect (34, 35). 



f) Facilitation and Fatigue. A rather general phenomenon of synaptic trans- 

 mission is that now termed presynaptic (or posttetanic) facilitation. Autonomic 

 ganglia (121, 137) and eel electroplaques (4-6) for a long time after a single 

 presynaptic stimulus (fig. 2) exhibit enhanced responsiveness to another stimu- 

 lus, through the same homosynaptic pathway, but not to another (hetero- 

 synaptic) pathway or to direct stimulation. There are no persistent changes in 

 membrane potential to accompany the enhancement of responsiveness (4). In 

 other systems (79, 139) the facilitation is manifested best when the presynaptic 

 nerve is stimulated at high rates and for long times. One explanation offered for 

 this phenomenon is that the presynaptic electrical response becomes more effec- 

 tive for releasing the transmitter agent, a greater quantity of the latter becom- 

 ing available at the synapse perhaps because the presynaptic spikes starts from 

 a baseline of hyperpolarization after the previous activity and is therefore 

 higher in amplitude. The facilitating action is therefore presumed to reside in 

 the presynaptic fiber. Another possibility is that the conditioning stimulation 

 has left behind at the synapse a residue of the transmitter or of the changed 

 state of the transducer molecules which raises the synaptic effectiveness of 

 subsequently emitted transmitters. This view (4) places the facilitatory action 

 at the postsynaptic membrane, but localized to those synapses previously 

 excited and not affecting other, probably even nearby synaptic membrane 

 regions. 



The reverse phenomenon of synaptic 'fatigue' is also rather general. Repeti- 

 tive stimulation of the presynaptic pathway leads to transmission block, al- 

 though a smaller p.s.p. is usually still elicited (e.g., squid giant axon; ref. 25). 

 The post-junclional cell remains, however, directly excitable (4, 25). The block 

 might result from absolute or relative exhaustion of the store of transmitter at 

 the presynaptic terminals, from secondary, depressant effects elicited by excess 

 of the transmitter, or from secondary changes in the transducer molecules 

 analogous to 'sodium inactivation' of squid giant axons. This phenomenon is 



