NMDA CHANNEL REGULATION BY CHANNEL-ASSOCIATED PROTEIN-TYROSINE KINASESRC

The N-methyl-D-aspartate (NMDA) receptor mediates synaptic transmissio n and plasticity in the central nervous system (CNS) and is regulated by tyrosine phosphorylation. In membrane patches excised from mammalia n central neurons, the endogenous tyrosine kinase Src was shown to reg ulate the activity of NMDA channels. The action of Src required a sequ ence [Src(40-58)] within the noncatalytic, unique domain of Src. In ad dition, Src coprecipitated with NMDA receptor proteins. Finally, endog enous Src regulated the function of NMDA receptors at synapses. Thus, NMDA receptor regulation by Src may be important in development, plast icity, and pathology in the CNS.