The mechanism of action of diphenylhydantoin on invertebrate neurons. II. Effects on synaptic mechanisms.

The effect of diphenylhydantoin (DPH) on certain synapses of neurons in the abdominal ganglion of Aplysia and on the gamma-aminobutyric acid (GABA) mediated inhibitory synapse of the crayfish stretch receptor neuron (SRN) has been studied. DPH decreases the amplitude of the excitatory postsynaptic potential, but is ineffective on the "short" ACh mediated, Cl- dependent, inhibitory postsynaptic potential (IPSP) in Aplysia. However, it facilitates the "long" ACh mediated, K+ dependent, IPSP, in this same group of neurons. DHP has a profound effect on the GABA mediated, Cl- dependent, inhibitory synapse of the SRN. The time course of the IPSP is prolonged up to 10 times control values, due to an increased and prolonged postsynaptic conductance. Similar results have been obtained in the SRN with iontophoretic application of GABA. This selective effect of DPH on synaptic mechanisms, especially in view of the role of GABA and ACh as putative transmitters in the mammalian nervous system, may play an important role for the anticonvulsant action of DPH.