RAPID EFFECTS OF KAINATE ADMINISTRATION ON ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONIC-ACID (AMPA) RECEPTOR PROPERTIES IN RAT HIPPOCAMPUS

We investigated changes in AMPA receptor properties in rat hippocampus 5 h after systemic kainate administration. Quantitative [H-3]AMPA aut oradiography and Western blot analysis of receptor subunits GluR1-3 in different subcellular fractions were used to evaluate possible altera tions in binding characteristics and immunological properties of the r eceptors in synaptic and nonsynaptic fractions. Both ligand-binding an d Western blots revealed significant changes in binding and immunologi cal properties of nonsynaptic receptors but relatively smaller changes in synaptic receptors 5 h after kainate administration. GluR2/3 showe d a greater relative change in the synaptic receptor population compar ed to GluR1, suggesting either a shift in subunit composition of AMPA receptors or the formation of a synaptic subpopulation of AMPA recepto rs with truncated C-terminal domain of GluR1 subunits. The effects of kainic acid were blocked by cycloheximide treatment indicating that th e changes were due at least in part to increased synthesis of AMPA rec eptor subunits. The results indicate that excessive synaptic activity produces rapid changes in both synaptic and nonsynaptic AMPA receptor properties. (C) 1998 Academic Press.