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

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Abstract
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 neuron of the isolated crayfish stretch receptor. The soma was penetrated with 2 micro-electrodes to allow accurate determination of membrane conductances. 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. The pharmacological properties of the 2 drugs are unlikely to be mediated by effects on cationic movements in this preparation. DPH increased the amplitude and duration of the inhibitory post-synaptic potential (IPSP) within the range 10-9 to 10-4 M. The response to ionophoretically applied GABA was similarly prolonged. PTX decreased the amplitude of the IPSP and prolonged its rising phase within the range 10-8 to 10-4 M. The response to ionophoretically applied GABA was similarly depressed. 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. The action of both drugs is post-synaptic and suggests that DPH decreases the probability of closing, and PTX the probability of opening, of the transmitter-activated channels. The lack of any structural similarity between the 2 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.