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HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



it does on crayfish stretch receptor membrane by 

 eHminating the depolarizing electrogenesis (fig. 24). 

 However, when GABA is applied to the cerebral 

 cortex, its selective elimination of depolarizing 

 surface-negative p.s.p.'s discloses the previously 

 masked hyperpolarizing surface-positive p.s.p.'s. 

 Acting in the cerebral cortex (figs. 22, 24) GABA 

 and its congeners invert the electrocortical activity 

 evoked by a stimulus. 



The effects of the .selective inactivators of hyper- 

 polarizing synapses, Ce and Cg (fig. 23), also differ 

 depending upon the type of electrogenic structure 



20 MSEC 



FIG. ^4. Different effects of the selective inactivator of de- 

 polarizing p.s.p.'s at different sites. A, t to 5.- Simultaneous re- 

 cordings from the cerebral cortex with a large surface electrode 

 (upper trace) and a fine wire electrode (lower trace). /, both 

 electrodes were on the surface and recorded nearly identically 

 the evoked surface negative p.s.p.'s of the superficial cerebral 

 dendrites. 2, the fine electrode was inserted about 0.4 mm be- 

 low the surface into an essentially isoelectric region. 3 and 4, 

 application of GABA to the cortical surface reversed the surface 

 response into positivity, but this change did not appear in the 

 subsurface recording. This indicates that the effect produced by 

 the amino acid was on superficial p.s.p.'s only, j, rinsing the 

 cortical surface restored the original activity at the surface. The 

 subsurface recording was still unchanged. 6, superimposed 

 responses before and during the action of G.^B.'K. B: The simul- 

 taneous recordings in this experiment were from the cerebral 

 cortex (upper trace) and the cerebellar (lower trace). /, before 

 applying GABA; 2, five drops of 0.1 per cent G,'\B.'\ were ap- 

 plied to each site. In the cerebral cortex the result was a reversal 

 of surface potential. In the cerebellar cortex the surface nega- 

 tivity was eliminated by blockade of the depolarizing p.s.p.'s, 

 but no positivity developed because of the paucity of hyper- 

 polarizing synapses in this structure. 3, recovery was rapid in 

 the cerebral and slower in the cerebellar cortex. Time, 20 msec. 

 [From Purpura et al. (163).] 



that is used as a test object. Neither the crayfish 

 stretch receptor nor the cerebellar cortex is affected 

 by application of co-aminocaprylic acid (Cj). How- 

 ever, the surface negativity evoked in the cerebral 

 cortex is augmented by the blockade which Ce and 

 Cs cause amongst the surface-positive p.s.p.'s of the 

 hyperpolarizing synapses. 



Recent work (Grundfest et al., in preparation; cf. 

 99, 163) indicates that the axodendritic synaptic 

 membrane in the cat brain stands in a doubly in- 

 verted pharmacological relation with some crusta- 

 cean synapses. GABA and other inactivators of the 

 cat depolarizing synapses activate crustacean in- 

 hibitory synapses. Picrotoxin, an activator of cat 

 excitatory synapses, inactivates the crustacean 

 inhibitory synapses. One of the selective inactivators 

 of cat inhibitory synapses, carnitine (cf. 163), activates 

 the excitatory synapses of lobster muscle fibers. 

 However, these inverted parallels are not complete. 

 The Ce and Cs co-amino acids do not affect the 

 crustacean synapses. Likewise, acetylcholine, d-luho- 

 curarine and strychnine are without effect. 



In sum, it may be concluded from the foregoing 

 discussion that determination of the mode of action 

 of a drug depends not only on the degree of intimate 

 knowledge which may be obtained of its synaptic 

 effects but also upon the type of information that 

 may be provided by the test object. The synaptic 

 structure u.sed for the tests may be too complex to 

 yield the details required, but also it may be too 

 simple and provide only misleadingly partial in- 

 formation. 



Identification and Characterization oj Transmitter Agents 



The preceding section sets the theoretical and 

 methodological background for the problems treated 

 in this. The quantity of transmitters released during 

 activity of presynaptic terininals is probably ex- 

 ceedingly small (cf. 52, 59, 60, 68). The problem of 

 their identification therefore is strongly conditioned 

 by methodology. For example, norepinephrine has 

 been known, since its laboratory synthesis in 1904 

 (cf. 193), to have properties similar to those of its 

 homologue, epinephrine. Also, the work of Cannon 

 and his associates (cf. 1 77) had indicated very 

 clearly that there must be at least several sym- 

 pathetic transmitters which were designated as 

 sympathins E (excitatory) and I (inhibitory). Never- 

 theless, norepinephrine was not accepted as a pos- 

 sible sympathetic transmitter until it was shown in 

 1946 (cf 193) that it is a natural constitutent of the 



