INHIBITORY TRANSMITTERS — A REVIEW 361 



peripheral nerve prepared in the same way as Factor I extracts (Florey, 

 1956), or GAB A (Florey, 1957). Furthermore the actions both of appUed 

 materials and of inhibitory nerve stimulation are prevented by picrotoxin, 

 which there is reason to believe acts in these animals in much the same way 

 as do low concentrations of strychnine in the vertebrates (Florey, 1951). The 

 suggestion is strong then that the active material of Factor I (and the material 

 in the crustacean nerve extracts) acts as an inhibitor of synaptic processes in 

 the heart ganglion. The question of its possible identity with GABA will be 

 further discussed below. 



CRUSTACEAN STRETCH RECEPTORS 



The thoracic and abdominal stretch receptor organs of crayfish, the 

 detailed anatomy of wliich has been described by Florey and Florey (1955), 

 have been extensively used as assay preparations in the work on Factor I, 

 but have also been important in the study of the inhibitory process itself. 

 The sensory neurons of the stretch receptors receive a direct peripheral 

 inhibitory innervation, and the effects of stimulation of this fibre can be 

 recorded from the two neurons of each organ. 



The electrical events associated with this inhibitory process have been 

 studied by Kufiler and his colleagues. They have shown that the discharge of 

 the neuron is preceded by slow depolarization of the cell soma (the generator 

 potential) which must achieve a critical level for the spike discharge to occur 

 (Eyzaguirre and Kuffler, 1955). Stimulation of the inhibitory fibre brings 

 about a repolarization of the membrane such that the generator potential is 

 abolished and the cell prevented from firing (Kufiler and Eyzaguirre, 1955). 

 Alteration of the membrane potential demonstrates that the inhibitory 

 potential can be reversed in polarity, as was described above for i.p.s.p.'s 

 at motor neurons. An increased permeability to potassium ions, but appar- 

 ently not to chloride, is involved (Edwards and Hagiwara, 1959). 



The application of Factor I solutions to the stretch receptor neuron results 

 in cessation of their discharge (Florey, 1954) and this finding led to the use of 

 these organs as test and assay preparations in studies of Factor I. It was 

 through the use of this method that GABA was originally suggested as the 

 active constituent of Factor I (Bazemore et al, 1957) and it has in fact been 

 shown that the effect of GABA closely mimics the action of stimulation of the 

 inhibitory axon (Kufiler and Edwards, 1958). The application of GABA 

 results in an hyperpolarization of the cell, prevents the production of the 

 sensory discharge, and. as is shown in Fig. 6, reduces the size of an evoked 

 inhibitory potential. The significance of this last observation has been con- 

 sidered above in relation to the i.p.s.p. The suggestion that GABA is the 

 transmitter substance released on stimulation of these inhibitory axons is 

 thus very strong, yet as will be indicated later there is good reason for beheving 



