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 (I_Ca) 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 (I_Cl(Ca)). An Ano1-selective inhibitor Ani9 was less effective suggesting that Ano2 is the predominant I_Cl(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 (I_Cl(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 I_Cl(Ca), consistent with contributions to feedback from both I_Cl(Ca) and I_Cl(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⁺].