Depolarization of retinal horizontal cells by excitatory amino acid neurotransmitter agonists

We have recorded the intracellular membrane potential of horizontal cells, second-order interneurones of the vertebrate retina, from fish retinae perfused with Ringer solution containing agonist drugs of the excitatory neurotransmitters, L-glutamate and L-aspartate. We show that at concentrations greater than about 10 microM, kainate and quisqualate have a potent depolarizing effect on horizontal cells and suppress their light evoked electrical responses (S-potentials). In contrast, a third agonist, N-methyl-D-aspartate, hyperpolarizes horizontal cells. The depolarizing action of kainate and quisqualate persists in the presence of the synaptic blocker, cobalt chloride, which implies that they bind directly on the horizontal cell membranes. Two kainate-related drugs, which are active on invertebrate neurones, were also examined, one, alpha-ketokainate, simulates the action of kainate, but the other, dihydrokainate, is ineffective on horizontal cells. L-Glutamate binds with high affinity at quisqualate sites, whereas L-aspartate binds with high affinity at NMDA sites, thus we conclude that L-glutamate is the likely neurotransmitter at the photoreceptor-horizontal cell synapse.