REGULATORY PHOSPHORYLATION OF AMPA-TYPE GLUTAMATE RECEPTORS BY CAM-KII DURING LONG-TERM POTENTIATION

Longterm potentiation (LTP), a cellular model of learning and memory, requires calcium-dependent protein kinases. Induction of LTP increased the phosphorus-32 labeling of lpha-amino-3-hydroxy-5-methyl-4-isoxazo lepropionic acid (AMPA)-type glutamate receptors (AMPA-Rs), which medi ate rapid excitatory synaptic transmission. This AMPA-R phosphorylatio n appeared to be catalyzed by Ca2+- and calmodulin-dependent protein k inase II (CaM-KII): (i) it correlated with the activation and autophos phorylation of CaM-KII, (ii) it was blocked by the CaM-KII inhibitor K N-62, and (iii)its phosphorus-32 peptide map was the same as that of G luR1 coexpressed with activated CaM-KII in HEK-293 cells. This covalen t modulation of AMPA-Rs in LTP provides a postsynaptic molecular mecha nism for synaptic plasticity.