Modulation of excitatory synaptic transmission by drugs that reduce desensitization at AMPA/kainate receptors.
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.
Section of Neurophysiology and Biophysics, NICHD, National Institutes of Health, Bethesda, Maryland 20892.
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Vyklicky
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Patneau
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Mayer
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006624:Hippocampus / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013395:Sucrose / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014909:Wheat Germ Agglutinins
D003208:Concanavalin A; D005971:Glutamates; D018698:Glutamic Acid; D011760:Pyrrolidinones; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter; D013395:Sucrose; D014909:Wheat Germ Agglutinins; C036466:aniracetam