Slow desensitization regulates the availability of synaptic GABA(A) receptors.
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.
Overstreet
L S
LS
Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA. overstre@ohsu.edu.
Jones
M V
MV
Westbrook
G L
GL
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D058785:GABA-A Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D026901:Membrane Transport Proteins; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009557:Nipecotic Acids / Q000494:pharmacology; D027361:Organic Anion Transporters; D010091:Oximes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D002352:Carrier Proteins; D018755:GABA Agonists; D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D058785:GABA-A Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; D010091:Oximes; D011963:Receptors, GABA-A; C078793:NNC 711; D005680:gamma-Aminobutyric Acid