GABAA and GABAC receptors in adult porcine cones: evidence from a photoreceptor-glia co-culture model.

1. Edge contrast enhancement is an integrated visual function based on the complex centre-surround organization of the cone photoreceptor light response. While centre responses result from direct light activation, surround responses are thought to result from lateral inhibition mediated by horizontal cells. This feedback signal has been attributed to GABAA receptors which have been found in lower vertebrate cones. 2. In order to study the GABA response of adult mammalian photoreceptors, we designed a culture system consisting of isolated photoreceptors seeded on a layer of retinal glial cells. Mature rods and cones required the presence of Muller glial cells to survive and develop neurites; they degenerated in the absence of glial cells. 3. Cone photoreceptors generated large GABA responses whereas rod photoreceptors did not respond to GABA applications. 4. Cone GABA responses consisted of two distinct components, one suppressed by the GABAA receptor blockers bicuculline and SR95531, and the second by the GABAC receptor antagonists TPMPA and imidazole-4-acetic acid (I4AA). Pentobarbital greatly increased the GABAA receptor component whereas it did not affect, or even reduced, the GABAC receptor component. During long GABA applications, GABAA receptor currents desensitized by 78%, contrasting with the sustained GABAC response. 5. Expression of GABAC receptors in cone photoreceptors was confirmed by anti-rho-subunit immunolabelling of porcine retinal sections. 6. These results indicate that both GABAA and GABAC receptors may participate in the feedback synapse from horizontal cells to cone photoreceptors in the mammalian retina.