Synaptically released glutamate does not overwhelm transporters on hippocampal astrocytes during high-frequency stimulation

J Neurophysiol. 2000 May;83(5):2835-43. doi: 10.1152/jn.2000.83.5.2835.


In addition to maintaining the extracellular glutamate concentration at low ambient levels, high-affinity glutamate transporters play a direct role in synaptic transmission by speeding the clearance of glutamate from the synaptic cleft and limiting the extent to which transmitter spills over between synapses. Transporters are expressed in both neurons and glia, but glial transporters are likely to play the major role in removing synaptically released glutamate from the extracellular space. The role of transporters in synaptic transmission has been studied directly by measuring synaptically activated, transporter-mediated currents (STCs) in neurons and astrocytes. Here we record from astrocytes in the CA1 region of hippocampal slices and elicit STCs with high-frequency (100 Hz) stimulus trains of varying length to determine whether transporters are overwhelmed by stimuli that induce long-term potentiation. We show that, at near-physiological temperatures (34 degrees C), high-frequency stimulation (HFS) does not affect the rate at which transporters clear glutamate from the extrasynaptic space. Thus, although spillover between synapses during "normal" stimulation may compromise the absolute synapse specificity of fast excitatory synaptic transmission, spillover is not exacerbated during HFS. Transporter capacity is diminished somewhat at room temperature (24 degrees C), although transmitter released during brief, "theta burst" stimulation is still cleared as quickly as following a single stimulus, even when transport capacity is partially diminished by pharmacological means.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / metabolism*
  • Amino Acid Transport System X-AG
  • Animals
  • Aspartic Acid / analogs & derivatives
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Biological Transport
  • Cells, Cultured
  • Drug Synergism
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / physiology
  • Glutamic Acid / metabolism*
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Kainic Acid / analogs & derivatives
  • Kainic Acid / pharmacology
  • Patch-Clamp Techniques
  • Purinergic P1 Receptor Antagonists
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Purinergic P1 / metabolism
  • Synapses / metabolism*
  • Synaptic Transmission / physiology
  • Theophylline / analogs & derivatives
  • Theophylline / pharmacology


  • ATP-Binding Cassette Transporters
  • Amino Acid Transport System X-AG
  • Purinergic P1 Receptor Antagonists
  • Receptors, AMPA
  • Receptors, Metabotropic Glutamate
  • Receptors, Purinergic P1
  • 3-hydroxyaspartic acid
  • Aspartic Acid
  • 8-cyclopentyl-1,3-dimethylxanthine
  • Glutamic Acid
  • dihydrokainic acid
  • Theophylline
  • Kainic Acid