Different sensitivities of NMDA receptor channel subtypes to non-competitive antagonists

Four kinds of heteromeric N-methyl-D-asparate (NMDA) receptor channels, the el, e2, e3 and e4 channels, were expressed in Xenopus oocytes and their sensitivities to various non-competitive antagonists were examined. The el and e2lt channels were more sensitive to (+)MK-801 (dizocilpine) than the e3 and e4 channels, whereas the sensitivities to phencyclidine (PCP), ketamine and iV-allylnormetazocine (SKF-10, 047) were only slightly variable among the four channels. Furthermore, the replacement by glutamine or arginine of the conserved asparagine residue in segment M2 of the e2 and NMDA receptor channel subunits reduced the sensitivities to PCP, ketamine and SKF-10, 047, though to different extents. These results, together with previous findings, suggest that these non-competitive antagonists as well as (+)MK-801 and Mg2+ act on a common site.