INHIBITORY TRANSMITTERS — A REVIEW 



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Fig. 1. Inhibitory postsynaptic potentials recorded from a biceps-semitendinosus 

 motor neuron {lower trace) elicited by increasing strength of stimulation of 

 quadriceps nerve {upper trace). Downward deflexion in the motor neuron records 

 indicates membrane hyperpolarization (Coombs et al., 1955c). (Courtesy of Sir 

 John Eccles and the Journal of Physiology.) 



of — 80mV, and that the current responsible for it is carried by an inward 

 movement of chloride and, less importantly, by an outward movement of 

 potassium ions, these fluxes taking place through the membrane underlying 

 the synaptic endings (Coombs et al, 1955a). 



The equihbrium potential for the i.p.s.p. was estimated in experiments 

 wherein the resting potential of the cell was artificially altered by the passage 

 of a steady background current, and the effect upon an evoked i.p.s.p. 

 observed. A typical series of records is shown in Fig. 2. When the resting 

 potential was set at 82 mV, the i.p.s.p. almost disappeared. If the resting 

 potential was less than this, the i.p.s.p. was an hyperpolarizing response; if 

 the resting potential was greater than 80 mV the i.p.s.p. was depolarizing, 

 and in both cases the farther the resting potential was from 80 mV the greater 

 the amphtude of the evoked change (Coombs et al, 1955a). 



The i.p.s.p. upon which I have concentrated here is to be contrasted with 

 the analogous potential change brought about in the cell by stimulation of an 

 excitatory pathway. In this case the transient potential reduces the resting 

 potential of the cell, and if the reduction is large enough will cause an all-or- 

 nothing spike discharge to occur. It has been named an excitatory postsynap- 

 tic potential (e.p.s.p.): its amphtude again depends upon the strength of 

 afferent stimulation, its equihbrium potential is about mV and its time 

 course is similar to that of the i.p.s.p.'s shown in Fig. 1 (Coombs et al., 

 1955b). The arithmetic sum of the depolarizations produced by e.p.s.p.'s 

 and the hyperpolarizations of the i.p.s.p.'s will determine the state of excit- 

 ability of the postsynaptic cell. It can be presumed that essentially similar 

 processes underly the excitation and inhibition of other types of neurons 

 within the central nervous system, and that the effects which I have described 

 are not mechanisms peculiar to motor neurons. 



From these observations, then, criteria for the action of an inhibitory 

 transmitter substance can be set up (Curtis et al., 1959). (1) If a substance be 

 artificially apphed to a postsynaptic cell it must mimic the action of stimula- 

 tion of an afferent pathway which, if the pathway is an inhibitory one must 



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