Dopamine enhances excitatory amino acid-gated conductances in cultured retinal horizontal cells

In the teleost retina, cone horizontal cells receive extensive innervation from dopaminergic interplexiform cells1, and possess dopamine receptors whose activation stimulates adenylate cyclase2,3. Exogenously applied dopamine modifies several aspects of horizontal cell activity in the intact retina, including the responsiveness of these neurons to light4–6 and the strength of electrical coupling between them7–9. We have used whole-cell voltage clamp methods to examine whether dopamine can alter the light-responsiveness of horizontal cells by changing their sensitivity to the neurotransmitter released by the photoreceptors. We report that dopamine and cyclic AMP, although having little direct effect on resting membrane conductance, greatly enhance ionic conductances gated by kainate, an agonist of the transmitter released by the photoreceptors, and by L-glutamate, the agent proposed to be the photoreceptor transmitter10–14. Our results provide the first direct evidence for dopaminergic regulation of excitatory amino-acid neurotransmission in the vertebrate nervous system and suggest a possible mechanism to explain the reduction in the responsiveness of horizontal cells observed when retinas are treated with dopamine.