Contributions of glutamate transporters and Ca2+-activated Cl- currents to feedback from horizontal cells to cone photoreceptors.

Lateral inhibitory feedback from horizontal cells (HCs) to cones establishes center-surround receptive fields and color opponency in the retina. When HCs hyperpolarize to light, inhibitory feedback to cones increases activation of cone Ca2+ currents (ICa) that can in turn activate additional currents. We recorded simultaneously from cones and HCs to analyze cone currents activated by HC feedback in salamander retina. Depolarization-activated inward tail currents in cones were inhibited by CaCCinh-A01 that inhibits both Ano1 and Ano2 Ca2+-activated Cl- currents (ICl(Ca)). An Ano1-selective inhibitor Ani9 was less effective suggesting that Ano2 is the predominant ICl(Ca) subtype in cones. CaCCinh-A01 inhibited feedback currents more strongly when intracellular Ca2+ in cones was buffered with 0.05 mM EGTA compared to stronger buffering with 5 mM EGTA. By contrast, blocking glutamate transporter anion currents (ICl(Glu)) with TBOA had stronger inhibitory effects on cone feedback currents when Ca2+ buffering was strong. Inward feedback currents ran down at rates intermediate between rundown of glutamate release and ICl(Ca), consistent with contributions to feedback from both ICl(Ca) and ICl(Glu). These results suggest that Cl- channels coupled to glutamate transporters help to speed inward feedback currents initiated by local changes in intracellular [Ca2+] close to synaptic ribbons of cones whereas Ano2 Ca2+-activated Cl- channels contribute to slower components of feedback regulated by spatially extensive changes in intracellular [Ca2+].