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

Recently, it has been shown that a single leucine-to-tyrosine mutation in t he agonist binding domains of the homomerically expressed alpha-amino-3-hyd roxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors GluR3 and GluR1 i s sufficient to completely block receptor desensitization. In the present s tudy we tested heteromeric subunit combinations of AM PA receptors to demon strate that the block of desensitization afforded by th is mutation is domi nant in heteromeric subunit complexes containing the leucine-to-tyrosine mu tation 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 AM PA receptors a re not linked to the editing state of the ion pore dom ain a nd thus are independent of the permeability properties of the ion cha nnel. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.