A role for GAT-1 in presynaptic GABA homeostasis?

Fiorenzo Conti, Marcello Melone, Giorgia Fattorini, Luca Bragina, Silvia Ciappelloni

Research output: Contribution to journalArticlepeer-review

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

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'A role for GAT-1 in presynaptic GABA homeostasis?'. Together they form a unique fingerprint.

Cite this