Action of glutamate and aspartate analogues on rod horizontal and bipolar cells

Electrophysiological evidence indicates that transmitter release from retinal rod terminals occurs at a high rate in the dark and is reduced by light1–6. The rod transmitter closes ionic channels (mainly sodium channels) in the subsynaptic membrane of a class of bipolar cells (on-centre bipolar cells) which depolarize in response to light4,7–9. However, the transmitter opens sodium channels in the subsynaptic membrane of horizontal cells4–6,9,10. We report here that several compounds, chemically related to the amino acids aspartate and glutamate, have similar post-synaptic actions to that of the rod neurotransmitter. Kainic acid11, in micromolar concentration, hyperpolarizes rod on-centre bipolar cells, increasing their membrane resistance while depolarizing rod horizontal cells. Experiments with 2-amino-4-phosphonobutyric acid (APB), in which a phosphono group is substituted for a carboxyl group of glutamic acid, have further distinguished between different binding sites on the cells which make synaptic contact with rods. APB is an agonist at the on-centre bipolar cells, closing the same ionic channels as the rod neurotransmitter, but is without effect on rod horizontal cells. The evidence presented here suggest that the widely held view that glutamate or aspartate is the rod neurotransmitter needs to be re-examined.

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