Modulation of excitatory synaptic transmission by drugs that reduce desensitization at AMPA/kainate receptors

Neuron. 1991 Dec;7(6):971-84. doi: 10.1016/0896-6273(91)90342-w.


Desensitization at AMPA/kainate receptors has been proposed to contribute to the decay of excitatory synaptic currents. We examined the action of aniracetam, wheat germ agglutinin (WGA), and concanavalin A (Con A), drugs that act via separate mechanisms to reduce desensitization evoked by L-glutamate in rat hippocampal neurons. The decay of excitatory synaptic currents, and sucrose-evoked miniature excitatory postsynaptic currents (EPSCs) was slowed 2- to 3-fold by aniracetam. In contrast, WGA increased the EPSC decay time constant only 1.3-fold and Con A had no effect. Aniracetam increased the magnitude of stimulus-evoked EPSCs 1.9-fold; variance analysis suggests a postsynaptic mechanism of action. WGA and Con A reduced EPSC amplitude via a presynaptic mechanism. Aniracetam increased the burst length of L-glutamate-activated single-channel responses. Simulations suggest that aniracetam either slows entry into a desensitized state or decreases the closing rate constant for ion channel gating.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Concanavalin A / pharmacology
  • Evoked Potentials / drug effects
  • Glutamates / pharmacology
  • Glutamic Acid
  • Hippocampus / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Pyrrolidinones / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*
  • Sucrose / pharmacology
  • Synapses / drug effects
  • Synapses / physiology*
  • Synaptic Transmission / drug effects*
  • Wheat Germ Agglutinins


  • Glutamates
  • Pyrrolidinones
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Receptors, Neurotransmitter
  • Wheat Germ Agglutinins
  • Concanavalin A
  • Glutamic Acid
  • Sucrose
  • aniracetam