A role for GAT-1 in presynaptic GABA homeostasis?

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In monoamine-releasing terminals, neurotransmitter transporters - in addition to terminating synaptic transmission by clearing released transmitters from the extracellular space - are the primary mechanism for replenishing transmitter stores and thus regulate presynaptic homeostasis. Here, we analyze whether GAT-1, the main plasma membrane GABA transporter, plays a similar role in GABAergic terminals. Re-examination of existing literature and recent data gathered in our laboratory show that GABA homeostasis in GABAergic terminals is dominated by the activity of the GABA synthesizing enzyme and that GAT-1-mediated GABA transport contributes to cytosolic GABA levels. However, analysis of GAT-1 KO, besides demonstrating the effects of reduced clearance, reveals the existence of changes compatible with an impaired presynaptic function, as miniature IPSCs frequency is reduced by one-third and glutamic acid decarboxylases and phosphate-activated glutaminase levels are significantly up-regulated. Although the changes observed are less robust than those reported in mice with impaired dopamine, noradrenaline, and serotonin plasma membrane transporters, they suggest that in GABAergic terminals GAT-1 impacts on presynaptic GABA homeostasis, and may contribute to the activity-dependent regulation of inhibitory efficacy.

Original languageEnglish
Pages (from-to)10
Number of pages1
JournalFrontiers in Cellular Neuroscience
Issue numberAPRIL
DOIs
Publication statusPublished - Apr 5 2011

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gamma-Aminobutyric Acid
Homeostasis
Membrane Transport Proteins
Neurotransmitter Transport Proteins
Cell Membrane
GABA Plasma Membrane Transport Proteins
Glutaminase
Glutamate Decarboxylase
Extracellular Space
Synaptic Transmission
Dopamine
Serotonin
Norepinephrine
GAT
Enzymes

Keywords

  • GABA
  • GABA transporters
  • GAT-1
  • Knock-out mice
  • mIPSCS

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

A role for GAT-1 in presynaptic GABA homeostasis? / Conti, Fiorenzo; Melone, Marcello; Fattorini, Giorgia; Bragina, Luca; Ciappelloni, Silvia.

In: Frontiers in Cellular Neuroscience, No. APRIL, 05.04.2011, p. 10.

Research output: Contribution to journalArticle

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