GABA transporters regulate a standing GABA_C receptor-mediated current at a retinal presynaptic terminal

At the axon terminal of goldfish retinal bipolar cells, GABA_C receptors have been shown to mediate inhibitory reciprocal synaptic currents. Here, we demonstrate a novel standing GABAergic current mediated exclusively by GABA_C receptors. Selective inhibition of GAT-1 GABA transporters on amacrine cells increases this tonic current and reveals a specific functional coupling between GAT-1 transporters and GABA_C receptors. We propose that this GABA_C receptor-mediated standing current serves to regulate synaptic gain by shunting depolarizing potentials that can produce Ca ²⁺-dependent action potentials at the bipolar cell terminal. Furthermore, we find that the amount of GABA_C receptor-mediated reciprocal feedback between bipolar cell terminals and amacrine cells is greatly increased when GAT-1 transporters are specifically blocked by NO-711 (1-[2-[[(diphenylmethylene)imino]oxy]ethyl]-1,2,5,6-tetrahydro-3- pyridinecarboxylic acid hydrochloride). The involvement of GAT-1 transporters in regulating this standing (or tonic) GABA_C current implicates them in a novel role as major determinants of presynaptic excitability.