SYNAPTIC AND EPHAPTIC TRANSMISSION 



167 



sites (52). The miniature p.s.p.'s are probably quanta! 

 in the sense that each is composed of a minimum 

 electrical change generated by a 'packet' of trans- 

 mitter agent. The random release of packets from 

 presynaptic terminals at different synaptic sites and 

 the electrical inexcitability of the postsynaptic mem- 

 brane combine to cause local miniature p.s.p.'s gener- 

 ated now at one site, now at another (51). 



Depolarization of the presynaptic nerve terminals 

 augments the frequency of miniature e.p.p.'s in frog 

 muscle fibers (52). Similar data (137) on rat dia- 

 phragm muscle are even more decisive (fig. 1 7). 

 Depolarizing electrotonus applied to the phrenic 

 nerve increases the rate of the miniature activity very 

 markedly, while hyperpolarizing the nerve terminals 

 decreases the activity. E.xcess magnesium, which de- 

 presses the release of transmitter agents (cf. 52), 

 depresses or eliminates the effects of the electrotonic 

 currents. 



The action of magnesium indicates that the effects 

 produced by the electrotonic potentials are exerted 

 through the medium of the nerve terminals and are 



100 



50 



c 

 c 

 o 



'- 5 



.»- Anodic Cathod'C -». 



FIG. 17. Effects upon the frequency of miniature e.p.p.'s in 

 rat diaphragm muscle fibers of electrotonus appHed to the 

 phrenic nerve. Abscissae show the intensity of applied electro- 

 tonic current in relative units; ordinates, the frequency of 

 miniature e.p.p.'s scaled logarithmically. Arrows point to 

 frequencies of the latter observed when no electrotonic currents 

 were applied. 'Cathodic' current is depolarizing for the nerve 

 terminals, anodic' is hyperpolarizing. A: The eflfects of the 

 change in potential were essentially symmetrical on the loga- 

 rithmic scale, increa.sed frequency of miniature e.p.p.'s with 

 cathodic and decreased frequency with anodic current. This 

 was the most frequently encountered result. B: open circles, 

 terminal depolarization was much more efTective than hyper- 

 polarization in changing the frequency in this experiment; 

 Jilled circles, the same inuscle was exposed to 12 mmole mag- 

 nesium (normal concentration is i mmole). The frequency of 

 miniature e.p.p.'s became essentially independent of the mem- 

 brane potential of the nerve fibers. [From Liley (137).] 



genuinely synaptic in nature. Other tests also lead to 

 this conclusion, a) The electrotonic effects on the 

 miniature e.p.p.'s are absent in muscle fibers where 

 the nerve supply is cut close to the muscle and thereby 

 made inaccessible to the electrotonic currents. This 

 rules out the possibility that the current flow in the 

 muscle fibers themselves caused the changed rate of 

 miniature e.p.p.'s. b') The effect of the electrotonus 

 was absent in endplates that were more than a few 

 millimeters from the site of applying the stimulus to 

 the nerve. Since the decay of electrotonically spread 

 potentials must be rapid in the terminal nerve fibers, 

 this result indicates that the change in rate is initiated 

 by effects in the presynaptic terminals. These experi- 

 ments show that when the depolarization produced 

 by a nerve impulse arrives at or near the presynaptic 

 terminals, their secretory activity can be initiated or 

 augmented. A mechanism coupling the presynaptic 

 impulse and transmission is thus provided. 



Some additional conclusions may be deduced from 

 data on miniature e.p.p.'s. These activities increase in 

 frequency approximately lo-fold for 15 mv depolari- 

 zation (137). Therefore a spike, though lasting only a 

 brief time, could mobilize the rapid release of a 

 considerable number of transmitter packets since 100 

 mv depolarization might increase the rate of ' spon- 

 taneous' releases some 10' to 10* times. The number 

 of packets involved in an e.p.p. during neuromuscular 

 transmission is probably about 10- to 10^ times the 

 'quantal' units that cause the miniature e.p.p.'s (52). 



Increase in the rate of release or .secretion of the 

 transmitter at the presynaptic terminals is obviously 

 an electrically activated event. However, the response 

 at the effector terminals probably differs Ijasically 

 from the processes that generate the spike of the con- 

 ductile membrane. The data of figure 1 7 were ob- 

 tained with prolonged applications of electrotonic 

 currents. The sustained increase of miniature e.p.p.'s 

 during sustained depolarization therefore indicates 

 that the processes leading to release of transmitter 

 packets are not subject to inactivation as is the sodium 

 conductance of the spike generator. 



Gradation of Postsynaptic Potentials 



Probably the miniature p.s.p.'s are small only be- 

 cause the area involved in their electrogenic activity 

 is small in comparison with the total area over which 

 the emf is electrotonically distributed. .Suppose that 

 we could measure the change in potential occurring 

 at a single isolated site which valves sodium ions. In 

 the resting state the emf across that site will be the 



