IDENTIFICATION OF A HIGH-AFFINITY BIVALENT CATION-BINDING SITE NEAR THE ENTRANCE OF THE NMDA RECEPTOR-CHANNEL

Single channel currents from recombinant N-methyl-D-aspartate (NMDA) r eceptors having an N-to-Q mutation in M2 reveal a divalent cation bind ing site that is near the entrance of the pore (similar to 0.2 through the electric field). Ca2+ rapidly binds to this site and readily perm eates the channel, while Mg2+ binds more slowly and does not permeate as readily. In wild-type receptors, Mg2+ also blocks the current by oc cupying a site that is similar to 0.6 through the field. When the more external site is occupied by Ca2+, the conductance of the pore to Na is reduced but not abolished, perhaps by an electrostatic blocking me chanism. The site serves to enrich the fraction of NMDA receptor curre nt carried by Ca2+.