INHIBITORY TRANSMITTERS— A REVIEW* 



H. McLennan 



Department of Physiology, University of British Columbia, Vancouver 



The concept of the transmission of excitation at synapses within the nervous 

 system, or at the junctions between neurons and effector organs, by means 

 of the release of a substance from the endings of the pre-junctional side is now 

 almost universally accepted. The same type of mechanism has logically been 

 invoked for synapses, activation of which gives rise to inhibition or depression 

 of the postsynaptic structure. It is the purpose of this paper to consider some 

 of the evidence which has been produced in support of certain substances 

 as possible mediators of transmission at these inliibitory synapses. I shall 

 consider first of all the situation pertaining to the vertebrate central nervous 

 system, and thereafter mention some peripheral inhibitory processes which 

 occur in vertebrates and in other animal species. 



The work of Eccles and his colleagues in Australia has provided the 

 ultimate criteria for assessment of any given compound as a possible trans- 

 mitter released at mammahan inhibitory synapses. From their work on the 

 neurons of the spinal cord, especially motor neurons, has emerged a picture 

 of the electrical changes brought about in a postsynaptic cell by activation 

 of an inhibitory pathway, and of the ionic mechanisms underlying these 

 electrical phenomena. It is worthwhile to summarize the findings at this point. 



When a spinal cord motor neuron is penetrated by a suitable microelec- 

 trode, a steady potential difference appears between the electrode tip and 

 that of an indifferent lead in contact with the extracellular fluid. When the 

 cell is at rest the magnitude of this potential difference is about 70 mV, inside 

 negative. Stimulation of an afferent pathway which functionally results in 

 inhibition of the motor neuron gives rise to a potential change superimposed 

 on the resting potential, and the ampfitude of this transient potential increases 

 as the intensity of the afferent stimulation is raised. Typical potentials of this 

 type recorded from a motor neuron, and which Coombs et al. (1955c) have 

 named inhibitory postsynaptic potentials (i.p.s.p.) are shown in Fig. 1. The 

 effect of stimulation of an inhibitory pathway then, is transiently to render 

 the inside of the cell more negative than is the case during rest. It has been 

 shown that the equifibrium potential for the i.p.s.p. is in the neighborhood 



* Aided by grants from the National Research Council of Canada and the Leon and 

 Thea Koemer Foundation. 



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