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

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

Research output: Contribution to journalArticlepeer-review

150 Scopus citations


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
Issue number21
StatePublished - Nov 1 2000


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

ASJC Scopus subject areas

  • Neuroscience(all)


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