NMDA RECEPTOR CHANNELS - SUBUNIT-SPECIFIC POTENTIATION BY REDUCING AGENTS

Sulfhydryl redox agents affect NMDA receptor activity. We investigated a putative redox site in four recombinant NMDA receptors. In 293 cell s expressing NR1-NR2A channels dithiothreitol (DTT) rapidly potentiate d L-glutamate-activated whole-cell currents and decreased the time cou rse of desensitization and deactivation. Part of the current potentiat ion (reversible component) and all kinetic changes reversed upon washo ut. The remaining potentiation (persistent component) was abolished by an oxidizing agent. The N-terminal 370 residues of NR2A mediate the r eversible component in chimeric NR2 subunits. In cells expressing the NR1-NR2B, -NR2C, and -NR2D channels DTT elicited only a slowly develop ing, persistent potentiation and increased the deactivation time cours e. In these, but not in NR1-NR2A, the DTT effect was rendered insensit ive to reoxidation by alkylation. Reduced glutathione mimicked the DTT effects only in the NR1-NR2A receptor. Hence, molecularly distinct NM DA receptors differ profoundly in their responses to sulfhydryl redox agents.