Kinetics and activation of postsynaptic kainate receptors at thalamocortical synapses: role of glutamate clearance

J Neurophysiol. 2001 Sep;86(3):1139-48. doi: 10.1152/jn.2001.86.3.1139.


Kainate (KA) receptor-mediated excitatory postsynaptic currents (EPSCs) exhibit slow kinetics at the great majority of synapses. However, native or heterologously expressed KA receptors exhibit rapid kinetics in response to agonist application. One possibility to explain this discrepancy is that KA receptors are extrasynaptic and sense glutamate diffusing from the synaptic cleft. We investigated this by studying the effect of three manipulations that change glutamate clearance on evoked KA EPSCs at thalamocortical synapses. First, we used high-frequency stimulation to increase extrasynaptic glutamate levels. This caused an apparent increase in the relative contribution of the KA EPSC to transmission and slowed the decay kinetics. However, scaling and summing the EPSC evoked at low frequency reproduced this, demonstrating that the effect was due to postsynaptic summation of KA EPSCs. Second, we applied inhibitors of high-affinity glutamate transport. This caused a depression in both AMPA and KA EPSC amplitude due to the activation of a presynaptic glutamatergic autoreceptor. However, transport inhibitors had no selective effect on the amplitude or kinetics of the KA EPSC. Third, to increase glutamate clearance, we raised temperature during recordings. This shortened the decay of both the AMPA and KA components and increased their amplitudes, but this effect was the same for both. Therefore these data provide evidence against glutamate diffusion out of the synaptic cleft as the mechanism for the slow kinetics of KA EPSCs. Other possibilities such as interactions of KA receptors with other proteins or novel properties of native synaptic heteromeric receptors are required to explain the slow kinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / pharmacology
  • Central Nervous System Stimulants / pharmacology
  • Cerebral Cortex / physiology*
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Glutamic Acid / metabolism*
  • Kainic Acid / analogs & derivatives*
  • Kainic Acid / pharmacology
  • Kinetics
  • Organ Culture Techniques
  • Picrotoxin / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Kainic Acid / physiology*
  • Synapses / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Temperature
  • Thalamus / physiology*


  • Central Nervous System Stimulants
  • Excitatory Amino Acid Antagonists
  • Receptors, Kainic Acid
  • Picrotoxin
  • 3-hydroxyaspartic acid
  • Aspartic Acid
  • Glutamic Acid
  • dihydrokainic acid
  • 2-Amino-5-phosphonovalerate
  • Kainic Acid