Ca2+ and H+ antagonize the decrease of [3H]MK-801 binding induced by glutamate and glycine in the presence of Mg2+.

We have studied the effects of various cations on [3H]MK-801 binding to N-methyl-D-aspartate (NMDA) receptors in membrane preparations of the rat cerebral cortex. Low concentrations of Tris, K+, Na+, Mg2+, and Ca2+ enhanced submaximally stimulated [3H]MK-801 binding. At high concentrations, all compounds inhibited [3H]MK-801 binding, possibly by a direct competitive effect. H+ decreased the observed association rate of [3H]MK-801 binding observed as a decreased [3H]MK-801 binding under nonequilibrium conditions, apparently by decreasing the sensitivity of the glutamate and glycine effects on the association rate. In addition, Tris, Na+, Mg2+, and possibly K+ at very high concentrations, permitted glutamate and glycine to decrease [3H]MK-801 binding, probably reflecting a decreased affinity of [3H]MK-801 binding. In contrast, Ca2+ and H+ antagonized these glutamate- and glycine-induced decreases of [3H]MK-801 binding observed in the presence of Mg2+, possibly by a direct competitive action on the permissive Mg2+ effect. These Ca2+ and H(+)-induced increases in [3H]MK-801 binding in the presence of Mg2+ may correspond to an increase in the potency of the Mg2+ block.