SYNAPTIC AND EPHAPTIC TRANSMISSION 



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FIG. 13. Differential effects of depolarization on the spike 

 and p.s.p. of the eel electroplaque. Column A to F, direct 

 stimulation i columns A' to F', etc., weak, moderately strong, 

 and very strong stimuli to a nerve. A to A'", the response of the 

 normal cell. The resting potential is about 80 mv seen as the 

 deflection of the active trace downward from the zero line 

 (upper trace). The strong direct stimulus evoked a spike with 

 very brief latency (.4). The weak neural volley caused a p.s.p. 

 CA'"), the stronger also a spike (.-!" and .-!'") arising out of the 

 p.s.p. The cell was treated with weak physostigmine (25 ^g per 

 ml solution) for 78 min., and weak acetylcholine (i ixg per mg) 

 for the last 58 min. of that period. These drugs had no effect 

 on the potentials; 5 ftg per ml acetylcholine were then added. 

 Depolarization developed, the spikes 36 min. later becoming 

 smaller, but the p.s.p. was unaffected (S to /?'"). The diminish- 

 ing electrically evoked response g min. later (C to C") became 

 graded, as seen by its larger size in response to the strong neural 

 volley. These effects progressed during the next ig min. (/) to 

 Z)'") and 1 1 min. thereafter (£ to £""). The p.s.p. to the 

 threshold neural volley decreased (£"). but was still evident 

 later (F') when the electiically excitable membrane no longer 

 responded to a much stronger direct stimulus (F). The p.s.p. 

 to a maximal neural stimulation (f ") was still about as large 

 as initially (^"')- This p.s.p. was capable of evoking a small 

 graded response of the electrically excitable membi^ane, as seen 

 by the delayed additional potential on the falling phase. [From 

 Altamirano el al. (6).] 



the magnitudes of the p.s.p.'s and also their signs may 

 be affected by changes in the membrane potential 

 (52, 60, 97). These effects, however, are secondary 

 and, indeed, are explicable only by the electrical 

 inexcitability of postsynaptic electrogenic membrane. 

 Suppose that a transducer action increases solely 

 the permittivity for CI~. More of this ion being present 

 in the external fluid, it tends to flow inward until the 

 increased internal negativity tends to prevent further 

 entry. Thus, the direction and amount of ionic flow 

 is determined both by the chemical concentration 



gradient and by the electrical potential gradient, the 

 coinbination being termed the electrochemical gradi- 

 ent. For a given concentration gradient there is a 

 corresponding potential gradient at which the flow 

 of ions is balanced by the opposite force of the elec- 

 trical charge. If the membrane resting potential is 

 increased by some means, the electrogenesis caused by 

 influx of Cl^ would reach the electrochemical poten- 

 tial (Ecr) for that ion sooner. The hyperpolarizing 

 p.s.p. would therefore appear to be smaller. If the 

 membrane potential is made more negative than Eci~, 

 Cl~ in the cell would be forced outward. The p.s.p. 

 would then appear to reverse in sign, depolarizing the 

 hyperpolarized membrane approximately to the level 

 of Eci~. This effect is seen in figure 14I. 



The p.s.p. can likewise be affected by changing the 

 Cl^ concentration either of the interior or of the 

 exterior. For example, suppose that the external Cl~ 

 is replaced by another anion which does not penetrate 

 the membrane. During transducer action, Cl~ would 

 move out from the cell since it is now more concen- 

 trated in the interior. The electrogenesis of hyper- 

 polarizing p.s.p.'s can thus be reversed to depolariza- 

 tion. The effect of increasing internal Cl~ is seen in 

 figure 14. Secondary electrochemical effects therefore 

 can change the amplitude or sign of the p.s.p. 



In the case of the depolarizing p.s.p.'s, increase of 

 resting membrane potential inay lead to increased 

 electrical responses; decrease of the resting potential 

 decreases and eventually reverses the sign of the de- 

 polarizing p.s.p.'s. These various conditions for 

 electrochemical grading and reversal of the p.s.p.'s 

 are found experimentally (figs. 4, 11, 14). The grading 

 and re\ersal of p.s.p.'s are strong evidence that the 

 tran.sducer actions of synaptic membrane are not 

 electrically excitable (97) since the physiological 

 responses are not affected even by violent changes of 

 the membrane potential, though the electrogenesis 

 itself is modified. 



Cat motoneuron p.s.p.'s are electrochemically 

 reversible (cf 60), but anomalies have been observed 

 that are instructive. In theory, as outlined above, the 

 apparent 'depolarization' of a reversed hyperpolariz- 

 ing p.s.p. should only return the membrane potential 

 to the saine level as does the hyperpolarization of the 

 normal p.s.p. The 'depolarization' therefore should 

 not reach the critical firing level for the spike, the 

 membrane in theory still remaining at a hyperpolar- 

 ized level, and the 'depolarizing' p.s.p. should not 

 become excitatory. Frequently, however, this is not 

 the case when the reversal is produced by changing 

 the ionic concentration gradients of the motoneuron. 



