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(C) 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 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.
Ichinose
Tomomi
T
Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Lukasiewicz
Peter D
PD
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009557:Nipecotic Acids / Q000494:pharmacology; D027361:Organic Anion Transporters; D010091:Oximes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D018079:Receptors, GABA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014562:Caudata; D014785:Vision, Ocular / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002352:Carrier Proteins; D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; C087200:GABA-C receptor; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; D010091:Oximes; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C078793:NNC 711; D005680:gamma-Aminobutyric Acid; D007608:Kainic Acid