364 H. MCLENNAN 



a change in the excitatory potentials ("simple", or /3-inhibition). The two 

 processes have been studied further by Fatt and Katz (1953) and by Hoyle 

 and Wiersma (1958). 



Fatt and Katz observed httle or no effect upon the level of polarization of 

 the muscle membrane produced by inhibitory nerve stimulation alone; how- 

 ever, if the membrane potential were altered by passage of current, inhibitory 

 potentials appeared which apparently had equilibrium potentials near 

 —75 mV. They observed also that, whether or not an inhibitory potential 

 was produced, there was a change in permeability of the membrane leading 

 to a more rapid decay of the excitatory junctional potentials. This resulted 

 in a diminished total depolarization during inhibitory action. Boistel and 

 Fatt (1958) concluded that an increased permeability to chloride ions occurred 

 in crayfish muscle during inhibitory action. 



Hoyle and Wiersma reported that stimulation of inhibitory fibres in cray- 

 fish, crabs and lobsters could lead to either depolarization or hyperpolariza- 

 tion of the cell (the equilibrium potential for the process in crayfish was about 

 — 58 mV) but that more often /3-inhibition was observed. 



Factor I solutions perfused through a crayfish claw prevent muscular 

 contraction on stimulation of the motor nerve (Florey, 1954). The effect has 

 been claimed to be duplicated by GABA (McLennan, 1957; Robbins, 1959) 

 and suitable administration of picrotoxin could prevent the GABA effect 

 (van der Kloot and Robbins, 1959). Boistel and Fatt (1958) and van der 

 Kloot and Robbins (1959) both concluded that GABA mimicked the action 

 of inhibitory nerve stimulation, when the stimulation gave rise to a-inhibition. 

 On the other hand Hoyle and Wiersma (1958) reported that the substance 

 failed to produce an increase in membrane potential in cases where inhibitory 

 nerve stimulation had this effect, and in no case caused mechanical in- 

 hibition. 



On the basis of the evidence presented in the foregoing sections there was 

 reason to believe that GABA was in fact the transmitter substance involved 

 in several inhibitory processes in Crustacea; and, as mentioned above, their 

 similarity of action on the crayfish stretch receptor neuron led to the sugges- 

 tion that GABA and Factor I were identical. It is therefore the more surprising 

 that Florey and Biederman (1960) have shown that inhibitory axons in the 

 legs of crabs and lobsters do not contain any detectable GABA, and the same 

 is apparently true also for the cardio-inhibitory fibres of crayfish (Florey, 

 1960). Florey has suggested the term Substance I for the active crustacean 

 material to differentiate it from the mammaUan Factor I. The actions of 

 Substance I, the transmitter released on activation of peripheral inhibitory 

 axons in Crustacea are thus duplicated by GABA, but the two materials are 

 not chemically identical. The chemical nature of Substance I, like that of 

 Factor I remains unknown. 



Thus the preparations which appear most likely to contain an inhibitory 



