Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A

Neuron. 1993 Dec;11(6):1069-82. doi: 10.1016/0896-6273(93)90220-l.

Abstract

Potentiation by cyclothiazide of recombinant glutamate receptor responses in Xenopus oocytes showed absolute selectivity for AMPA versus kainate receptors. In contrast, concanavalin A strongly potentiated responses at kainate but not AMPA receptors. Rapid desensitization in HEK 293 cells transfected with AMPA receptors was blocked by cyclothiazide, but only weakly attenuated by concanavalin A. Desensitization at kainate receptors was blocked by concanavalin A but unaffected by cyclothiazide. Selective effects of these modulators following coexpression of subunits from different families suggest independent assembly of functional AMPA and kainate receptors. Northern blot analysis of mRNA for dorsal root ganglia revealed a predominant expression of GluR5, indicating that modulation of desensitization by concanavalin A but not cyclothiazide in sensory neurons accurately predicts subunit expression for native glutamate receptors.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Benzothiadiazines / pharmacology*
  • Blotting, Northern
  • Cell Line
  • Cerebellum / metabolism
  • Cloning, Molecular
  • Concanavalin A / pharmacology*
  • Female
  • Ganglia, Spinal / metabolism
  • Gene Expression
  • Kinetics
  • Macromolecular Substances
  • Membrane Potentials / drug effects
  • Neurons / metabolism
  • Oocytes / drug effects
  • Oocytes / physiology
  • Prosencephalon / metabolism
  • RNA / isolation & purification
  • RNA / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / biosynthesis
  • Receptors, AMPA / drug effects*
  • Receptors, AMPA / physiology
  • Receptors, Glutamate / biosynthesis
  • Receptors, Glutamate / drug effects*
  • Receptors, Glutamate / physiology
  • Receptors, Kainic Acid / biosynthesis
  • Receptors, Kainic Acid / drug effects*
  • Receptors, Kainic Acid / physiology
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / drug effects
  • Recombinant Proteins / metabolism
  • Transfection
  • Xenopus laevis

Substances

  • Benzothiadiazines
  • Macromolecular Substances
  • Receptors, AMPA
  • Receptors, Glutamate
  • Receptors, Kainic Acid
  • Recombinant Proteins
  • Concanavalin A
  • RNA
  • cyclothiazide