A desensitization-inhibiting mutation in the glutamate binding site of rat alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunits is dominant in heteromultimeric complexes

Neurosci Lett. 1999 Dec 31;277(3):161-4. doi: 10.1016/s0304-3940(99)00885-x.


Recently, it has been shown that a single leucine-to-tyrosine mutation in the agonist binding domains of the homomerically expressed alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors GluR3 and GluR1 is sufficient to completely block receptor desensitization. In the present study we tested heteromeric subunit combinations of AMPA receptors to demonstrate that the block of desensitization afforded by this mutation is dominant in heteromeric subunit complexes containing the leucine-to-tyrosine mutation in at least one of the subunits. In addition, by comparing mutated, desensitization-deficient forms of unedited GluR1 and GluR1 edited at the Q/R-site of the ion pore we demonstrate that the desensitization properties of AMPA receptors are not linked to the editing state of the ion pore domain and thus are independent of the permeability properties of the ion channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Benzothiadiazines / pharmacology
  • Binding Sites / genetics
  • Female
  • Genes, Dominant
  • Glutamic Acid / metabolism*
  • Mutation / physiology*
  • Oocytes
  • Protein Isoforms / drug effects
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Editing
  • Rats
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / genetics*
  • Receptors, AMPA / metabolism*
  • Xenopus laevis


  • Benzothiadiazines
  • Protein Isoforms
  • Receptors, AMPA
  • Glutamic Acid
  • cyclothiazide
  • glutamate receptor ionotropic, AMPA 1