RGD Reference Report - Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter GAT-1. - Rat Genome Database

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Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter GAT-1.

Authors: Wu, Yuanming  Wang, Wengang  Díez-Sampedro, Ana  Richerson, George B 
Citation: Wu Y, etal., Neuron. 2007 Dec 6;56(5):851-65. doi: 10.1016/j.neuron.2007.10.021.
RGD ID: 152025510
Pubmed: PMID:18054861   (View Abstract at PubMed)
PMCID: PMC2156040   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neuron.2007.10.021   (Journal Full-text)

GABA transporters play an important but poorly understood role in neuronal inhibition. They can reverse, but this is widely thought to occur only under pathological conditions. Here we use a heterologous expression system to show that the reversal potential of GAT-1 under physiologically relevant conditions is near the normal resting potential of neurons and that reversal can occur rapidly enough to release GABA during simulated action potentials. We then use paired recordings from cultured hippocampal neurons and show that GABAergic transmission is not prevented by four methods widely used to block vesicular release. This nonvesicular neurotransmission was potently blocked by GAT-1 antagonists and was enhanced by agents that increase cytosolic [GABA] or [Na(+)] (which would increase GAT-1 reversal). We conclude that GAT-1 regulates tonic inhibition by clamping ambient [GABA] at a level high enough to activate high-affinity GABA(A) receptors and that transporter-mediated GABA release can contribute to phasic inhibition.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc6a1Ratgamma-aminobutyric acid:sodium:chloride symporter activity enablesIDA PMID:18054861UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Slc6a1  (solute carrier family 6 member 1)


Additional Information