Neuron
Volume 7, Issue 6, December 1991, Pages 971-984
Journal home page for Neuron

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

https://doi.org/10.1016/0896-6273(91)90342-WGet rights and content

Abstract

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.

References (38)

  • R.W. Aldrich et al.

    Voltage-dependent gating of single sodium channels from mammalian neuroblastoma cells

    J. Neurosci.

    (1987)
  • R.W. Aldrich et al.

    A reinterpretation of mammalian sodium channel gating based on single channel recording

    Nature

    (1983)
  • J.M. Bekkers et al.

    NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus

    Nature

    (1989)
  • J.M. Bekkers et al.

    Origin of variability in quantal size in cultured hippocampal neurons and hippocampal slices

  • J. Boulter et al.

    Molecular cloning and functional expression of glutamate receptor genes

    Science

    (1990)
  • D. Colquhoun et al.

    Fast events in singlechannel currents activated by acetylcholine and its analogues at the frog muscle end-plate

    J. Physiol.

    (1985)
  • J.C. Eccles et al.

    The relationship between the mode of operation and the dimensions of the functional regions at synapses and motor end-organs

  • G. el-Haji Fuleihan et al.

    Effects of the lectin concanavalin-A on the regulation of second messengers and parathyroid hormone release by extracellular Cal' in bovine parathyroid cells

    Endocrinology

    (1991)
  • I.D. Forsythe et al.

    Presynaptic glutamate receptors depress excitatory monosynaptic transmission between mouse hippocampal neurones

    J. Physiol.

    (1990)
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    L. V. and D. K. P. contributed equally to this study.

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