Activity-Dependent Phosphorylation of GLUR1/4 by PKA is Subunit Specific

Abstract

α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors are ionotropic glutamate receptors that mediate fast excitatory responses in neurons. Receptors containing subunits GluR1 or GluR4 are involved in the initial response to synaptic activity, and are known to be phosphorylated by protein kinase A (PKA) at serine residue 845 and 842, respectively. Through several experiments employing Western Blot analysis of rat hippocampal slices using phospho-specific antibodies, we have been able to determine how spontaneous synaptic activity affects this phosphorylation. The results show that synaptic activity does lead to the phosphorylation of GluR4 by PKA but does not regulate GluR1 phosphorylation. Additional results show that the number of phosphorylated GluR1 and 4 subunits increases with age. It is then suspected that although the cell may use these subunits for similar purposes, the biochemical regulation of their delivery to synapses may be different.