Potentiation by calcium ions of [3H]MK-801 binding to an ion channel associated with the N-methyl-D-aspartate receptor complex in rat brain.

In vitro addition of Ca2+ ions was effective in almost doubling binding of 3H-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) before equilibrium to an ion channel associated with an N-methyl-D-aspartate (NMDA)-sensitive subclass of brain excitatory amino acid receptors. The addition of inhibitors for phospholipase (PLase) A2 markedly reduced binding in the absence of added Ca2+ ions, while Ca2+ ions restored the reduction to the level found in the absence of the inhibitors. Pretreatment with PLases A2 and C but not D was effective in potentiating [3H]MK-801 binding in a biphasic manner at a concentration range of 5 mU/ml-10 U/ml. Moreover, PLases A2 and C at low concentrations not only suppressed the abilities of 3 different agonists to potentiate [3H]MK-801 binding before equilibrium, but also reduced that of Ca2+ ions. These results suggest that Ca2+ ions may potentiate [3H]MK-801 binding to the NMDA channel highly permeable to Ca2+ ions through a mechanism common to that underlying potentiation by exogenous PLase A2 and/or C.