Slow desensitization regulates the availability of synaptic GABA(A) receptors

L. S. Overstreet, M. V. Jones, Gary Westbrook

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

At central synapses, a large and fast spike of neurotransmitter efficiently activates postsynaptic receptors. However, low concentrations of transmitter can escape the cleft and activate presynaptic and postsynaptic receptors. We report here that low concentrations of GABA reduce IPSCs in hippocampal neurons by preferentially desensitizing rather than opening GABA(A) channels. GABA transporter blockade also caused desensitization by locally elevating GABA to ~1 μM. Recovery of the IPSC required several seconds, mimicking recovery of the channel from slow desensitization. These results indicate that low levels of GABA can regulate the amplitude of IPSCs by producing a slow form of receptor desensitization. Accumulation of channels in this absorbing state allows GABA(A) receptors to detect even a few molecules of GABA in the synaptic cleft.

Original languageEnglish (US)
Pages (from-to)7914-7921
Number of pages8
JournalJournal of Neuroscience
Volume20
Issue number21
StatePublished - Nov 1 2000

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GABA-A Receptors
gamma-Aminobutyric Acid
GABA Plasma Membrane Transport Proteins
Presynaptic Receptors
Synapses
Neurotransmitter Agents
Neurons

Keywords

  • Desensitization
  • GABA transporters
  • Hippocampus
  • Ligand-gated ion channel
  • mIPSC
  • Postsynaptic
  • Synaptic inhibition
  • Uptake blocker

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Slow desensitization regulates the availability of synaptic GABA(A) receptors. / Overstreet, L. S.; Jones, M. V.; Westbrook, Gary.

In: Journal of Neuroscience, Vol. 20, No. 21, 01.11.2000, p. 7914-7921.

Research output: Contribution to journalArticle

Overstreet, L. S. ; Jones, M. V. ; Westbrook, Gary. / Slow desensitization regulates the availability of synaptic GABA(A) receptors. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 21. pp. 7914-7921.
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