On the action of the anticonvulsant 5,5-diphenylhydantoin and the convulsant picrotoxin in crayfish stretch receptor.

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1. The effects of the anticonvulsant drug 5,5-diphenylhydantoin (DPH) and the convulsant drug picrotoxin (PTX) on various membrane properties and GABA-ergic inhibition were investigated in the slowly adapting neurone of the isolated crayfish stretch receptor. The soma was penetrated with two micro-electrodes to allow accurate determination of membrane conductances. 2. Neither DPH nor PTX at 10(-4) M had any significant effect on parameters of the anti- or orthodromic action potential or on the amplitude and duration of post-tetanic hyperpolarization. This suggests that the pharmacological properties of the two drugs are unlikely to be mediated by effects on cationic movements in this preparation. 3. DPH increased the amplitude and duration of the inhibitory post-synaptic potential (i.p.s.p.) within the range 10(-9) to 10(-4) M. The response to ionophoretically applied GABA was similarly prolonged. 4. PTX decreased the amplitude of the i.p.s.p. and prolonged its rising phase within the range 10(-8) to 10(-4) M. The response to ionophoretically applied GABA was similarly depressed. 5. A slow component of fluctuations in the resting potential was accentuated by DPH at 10(-4) M and eliminated by PTX 10(-4) M. This may reflect effects on the random opening and closing of inhibitory channels. 6. We conclude that the action of both drugs is post-synaptic and suggest that DPH decreases the probability of closing, and PTX the probability of opening, of the transmitter-activated channels. 7. The lack of any structural similarity between the two drugs suggests that they modify post-synaptic inhibition at separate sites. These sites appear to be interdependent since analysis of the shift in the DPH dose-response curve by PTX and vice versa, showed neither truly non-competitive nor competitive interaction.

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