The glutamate analog 2-amino-4-phosphonobutyrate antagonizes synaptic transmission from cones to horizontal cells in the goldfish retina

In the retina, the glutamate analog 2-amino-4-phosphonobutyrate (APB) distinguishes a class of glutamate receptors that is thought to be found only on depolarizing bipolar cells (DBCs). We now report that APB is a potent antagonist of cone-driven horizontal cells in the goldfish retina. APB hyperpolarized the membrane to the same potential as cobalt Ringer's and blocked the light responses. APB acted specifically on the cone pathway, as it had no effect on rod-driven horizontal cells. The lowest effective APB concentration for antagonistic action on the horizontal cells (approximately 2 microM) was similar to the concentration for agonist action on DBCs. APB was not able to block the actions of exogenous glutamate or kainate on horizontal cells. We propose that the action of APB on the cone-horizontal cell synapse is mediated at a site that is distinct from the glutamate and kainate binding site. Therefore, APB is most probably acting at a different locus on the synaptic glutamatergic receptors of the horizontal cells or at presynaptic receptors located on the cones themselves.