POTENTIATION BY CALCIUM-IONS OF [H-3] 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 bindin g of 0,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) befor e equilibrium to an ion channel associated with an N-methyl-D-aspartat e (NMDA)-sensitive subclass of brain excitatory amino acid receptors. The addition of inhibitors for phospholipase (PLase) A(2) markedly red uced binding in the absence of added CA(2+) ions, while Ca2+ ions rest ored the reduction to the level found in the absence of the inhibitors . Pretreatment with PLases A(2) and C but not D was effective in poten tiating [H-3]MK-801 binding in a biphasic manner at a concentration ra nge of 5 mU/ml-10 U/ml. Moreover, PLases A(2) and C at low concentrati ons not only suppressed the abilities of 3 different agonists to poten tiate [H-3]MK-801 binding before equilibrium, but also reduced that of Ca2+ ions. These results suggest that Ca2+ ions may potentiate [H-3]M K-801 binding to the NMDA channel highly permeable to Ca2+ ions throug h a mechanism common to that underlying potentiation by exogenous PLas e A(2) and/or C.