Rapid effects of kainate administration on α-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 autoradiography and Western blot analysis of receptor subunits GluR1-3 in different subcellular fractions were used to evaluate possible alterations in binding characteristics and immunological properties of the receptors in synaptic and nonsynaptic fractions. Both ligand-binding and Western blots revealed significant changes in binding and immunological properties of nonsynaptic receptors but relatively smaller changes in synaptic receptors 5 h after kainate administration. GluR2/3 showed a greater relative change in the synaptic receptor population compared to GluR1, suggesting either a shift in subunit composition of AMPA receptors or the formation of a synaptic subpopulation of AMPA receptors with truncated C-terminal domain of GluR1 subunits. The effects of kainic acid were blocked by cycloheximide treatment indicating that the changes were due at least in part to increased synthesis of AMPA receptor subunits. The results indicate that excessive synaptic activity produces rapid changes in both synaptic and nonsynaptic AMPA receptor properties. (C) 1998 Academic Press.