SYNAPTIC AND EPHAPTIC TRANSMISSION 



■77 



FIG. 22. Synaptic actions of shorter-chain u-amino acids. 

 Column A shows the response evoked in the cat cerebral cortex 

 by a local electrical stimulus (five superimposed traces indicate 

 the degree of variability). The surface negative potential (up- 

 ward deflection) is the p.s.p. of superficial dendrites. B shows 

 the effects of applying 0.2 cc of a i per cent buffered w-amino 

 acid. The substances are identified by the letters on the left 

 which correspond to those in table 4. .'Ml the compounds in- 

 verted the surface negativity to a surface positi\'ity by blocking 

 production of depolarizing p.s.p.'s and thereby disclosing hy- 

 perpolarizing p.s.p.'s which are recorded as surface positivity 

 (downward deflection). The action of all four substances was 

 similar but differed in magnitude and rate of onset, both factors 

 being largest with C, (GAB.A). Column C shows that recovery 

 from the action of the compounds is seen 3 min. after rinsing 

 the cortical surface several times with Ringer's solution. Time 

 at bottom, 20 msec. [From Purpura el al. (163).] 



synapse is inactivated. Il is for this reason that 

 selecti\e Ijlockade of inhibitory synapses by strych- 

 nine leads to excitatory' actions, augmented elec- 

 trical activity or convulsions. 



The selective action of many drugs on either hy- 

 perpolarizing or depolarizing synapses introduces an 

 important factor. A substance may act powerfully 

 on one synaptic .system and yet be inert with respect 

 to another which lacks the appropriate synaptic 

 substrate for the drug. This has been experimentally 

 verified with strychnine which is a highly selective 

 inactivator of hyperpolarizing inhibitory synapses 

 (fig. 14). Strychnine is inert, except in very high 

 concentrations, on structures like the muscle end- 



plate or the vermian cerebellar cortex of cat. How- 

 ever, when given in high concentration it does act 

 to blockade the depolarizing excitatory synapses 

 C166). 



In view of the foregoing, tests on relatively simple 

 synapses (table 2; figs. 11, 13, 15) may not be ade- 

 quate for analyzing drug actions. This fact is illus- 

 trated by the recent demonstration and analysis of 

 the synaptic actions of various amino acids (162, 

 163). The a)-amino acids tested (table 4), substances 

 in which the amino group is on the terminal carbon 

 farthest from the carboxyl radical, are selective in- 

 activators of cortical synapses. The shorter chain 

 compounds (C2 to C5, fig. 22) block depolarizing 

 activity of the dendrites while compounds Ce and 

 Cs (fig. 23) inactivate hyperpolarizing synapses. 



One of these substances, 7-aminobutyric acid 

 (GABA), occurs naturally in the brain (12, 173) and 

 has been identified (16) as a component of the 'in- 

 hibitory factor' which can be extracted from mam- 

 malian brain and which diminishes the discharge 

 of impulses in the mechanically excited crayfish 

 stretch receptor. As a selective blockader of de- 

 polarizing receptor and synaptic membrane, GABA 

 can only act as an ostensible 'inhibitor' when con- 

 fronted with the simple depolarizing electrogenic 

 membrane. Thus it acts on the cerebellar cortex as 



CAPROIC (Cg) 



FIG. 23. The qualitatively difl"erent effects produced by 

 w-amino acids with longer carbon chains. In each experiment, 

 responses were simultaneously evoked from the surface of the 

 cerebral cortex (upper trace) and cerebellar cortex (lower 

 trace). / and 4 show the responses in different experiments be- 

 fore applying the amino acids; 2 and 5, the cerebral p.s.p.'s 

 increased on applying C^ or Cg. The cerebellar activity was not 

 affected indicating that these u-amino acids are inert toward 

 the cerebellum. 3 and 6, responses after rinsing the cortical 

 surfaces with Ringer's solution. Time, 20 msec, is different in 

 the two experiments. Four traces superimposed in each record. 

 [From Purpura et al. (162).] 



