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PMID: 11050111 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 21 ·2000-11-01 ·Pages 7914-21

Overstreet LS, Jones MV, Westbrook GL

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 approximately 1 microm. 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.

MeSH Terms
Animals Biological Transport/drug effects Carrier Proteins/antagonists & inhibitors Cells, Cultured Dose-Response Relationship, Drug Excitatory Postsynaptic Potentials/drug effects GABA Agonists/pharmacology GABA Antagonists/pharmacology GABA Plasma Membrane Transport Proteins GABA-A Receptor Agonists GABA-B Receptor Antagonists Hippocampus/cytology,drug effects,metabolism In Vitro Techniques Ion Channel Gating/drug effects Membrane Proteins/antagonists & inhibitors Membrane Transport Proteins Neural Inhibition/drug effects,physiology Neurons/cytology,drug effects,metabolism Neurotransmitter Uptake Inhibitors/pharmacology Nipecotic Acids/pharmacology Organic Anion Transporters Oximes/pharmacology Patch-Clamp Techniques Rats Rats, Sprague-Dawley Receptors, GABA-A/metabolism Synapses/metabolism gamma-Aminobutyric Acid/metabolism,pharmacology
Chemicals
Carrier Proteins GABA Agonists GABA Antagonists GABA Plasma Membrane Transport Proteins GABA-A Receptor Agonists GABA-B Receptor Antagonists Membrane Proteins Membrane Transport Proteins Neurotransmitter Uptake Inhibitors Nipecotic Acids Organic Anion Transporters Oximes Receptors, GABA-A NNC 711 gamma-Aminobutyric Acid
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Overstreet L S
Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA. overstre@ohsu.edu.
Jones M V
Westbrook G L
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Email
overstre@ohsu.edu
Published
2000-11-01
Pages
7914-21
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772729
Subset
IM
Grants
NINDS NIH HHS · R01 NS026494 · United States
NIDA NIH HHS · T32 DA007262 · United States
NINDS NIH HHS · R01 NS26494 · United States
NIDA NIH HHS · T32 DA07262 · United States
External Links
PubMed source PMC Full Text View journal details
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