GABA transporters regulate inhibition in the retina by limiting GABA_C receptor activation

Inhibition is mediated by two classes of ionotropic receptors in the retina, GABA_A and GABA_C receptors. We used the GABA transport blocker NO-711 to examine the role of GABA transporters in shaping synaptic responses mediated by these two receptors in the salamander retinal slice preparation. Focal applications (puffs) of GABA onto GABA_A receptors on bipolar cells terminals or GABA_A receptors on ganglion cells elicited currents that were enhanced by NO-711, demonstrating the presence of transporters in the inner plexiform layer (IPL). IPSCs were evoked in bipolar and ganglion cells by puffing kainate into the IPL. NO-711 enhanced the IPSCs only in bipolar cells, suggesting that, when GABA uptake was blocked, the GABA_C receptors were more strongly activated by spillover transmission than the GABA_A receptors on ganglion ceils. N0 cells. NO-711 enhanced the light-evoked IPSCs mediated by GABA_C receptors on bipolar cell axon terminals, which resulted in reduced transmission between bipolar and ganglion cells. NO-711 also shifted the intensity-response relationship of the ganglion cell, reducing its sensitivity to light. Surround illumination has been shown by others to produce similar shifts in ganglion cell light sensitivity. Our results show that GABA transporters limit the extent of inhibitory transmission at the inner retina during light-evoked signal processing.