Cation interactions with putative NMDA receptor-gated channels labeled by [3H]MK-801 in rat cerebral cortex.

Polyvalent cations that block excitatory responses to N-methyl-D-aspartate inhibited the binding of [3H]MK-801 to putative N-methyl-D-aspartate receptor-gated channels in brain membranes. The order of potency was Zn2+ greater than La3+ = Cd2+ greater than Mn2+ greater than Co2+ greater than Ni2+ = Mg2+. These findings support the existence of interacting sites on the N-methyl-D-aspartate channel for ionic and organic antagonists, and provide a molecular mechanism for the modulation of excitatory neurotransmission and excitotoxicity by endogenous polyvalent cations.