GABA transporters regulate a standing GABAC 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 Ca2+-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.
Hull
Court
C
The Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239, USA.
Li
Geng-Lin
GL
von Gersdorff
Henrique
H
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D004553:Electric Conductivity; D004594:Electrophysiology; D050485:GABA Plasma Membrane Transport Proteins / Q000502:physiology*; D058805:GABA Uptake Inhibitors; D006054:Goldfish; D066298:In Vitro Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D018079:Receptors, GABA / Q000502:physiology*; D012160:Retina / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000502:physiology
D050485:GABA Plasma Membrane Transport Proteins; D058805:GABA Uptake Inhibitors; C087200:GABA-C receptor; D018079:Receptors, GABA; D002118:Calcium