GABA(A) and GABA(C) 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 respon se. While centre responses result from direct light activation, surround re sponses are thought to result from lateral inhibition mediated by horizonta l cells. This feedback signal has been attributed to GABA, receptors which have been found in lower vertebrate cones. 2. In order to study the GABA response of adult mammalian photoreceptors, w e designed a culture system consisting of isolated photoreceptors seeded on a layer of retinal glial cells. Mature rods and cones required the presenc e of Muller glial cells to survive and develop neurites; they degenerated i n the absence of glial cells. 3. Cone photoreceptors generated large GABA responses whereas rod photorece ptors did not respond to GABA applications. 4. Cone GABA responses consisted of two distinct components, one suppressed by the GABA(A) receptor blockers bicuculline and SR95531, and the second b y the GABA(C) receptor antagonists TPMPA and imidazole-4-acetic acid (I4AA) . Pentobarbital greatly increased the GABA, receptor component whereas it d id not affect, or even reduced, the GABA, receptor component. During long G ABA applications, GABA(A) receptor currents desensitized by 78%, contrastin g with the sustained GABA(C) response. 5. Expression of GABA(C) receptors in cone photoreceptors was confirmed by anti-rho -subunit immunolabelling of porcine retinal sections. 6. These results indicate that both GABA(A) and GABA(C) receptors may parti cipate in the feedback synapse from horizontal cells to cone photoreceptors in the mammalian retina.