Identification of a high affinity divalent cation binding site near the entrance of the NMDA receptor channel.
Single channel currents from recombinant N-methyl-D-aspartate (NMDA) receptors having an N-to-Q mutation in M2 reveal a divalent cation binding site that is near the entrance of the pore (approximately 0.2 through the electric field). Ca2+ rapidly binds to this site and readily permeates the channel, while Mg2+ binds more slowly and does not permeate as readily. In wild-type receptors, Mg2+ also blocks the current by occupying a site that is approximately 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 mechanism. The site serves to enrich the fraction of NMDA receptor current carried by CA2+.
Premkumar
L S
LS
Department of Biophysical Sciences, State University of New York at Buffalo 14214, USA.
Auerbach
A
A
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002413:Cations, Divalent; D004553:Electric Conductivity; D005260:Female; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism* / Q000494:pharmacology; D008564:Membrane Potentials; D051379:Mice; D016296:Mutagenesis; D009865:Oocytes; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D014982:Xenopus laevis
D002413:Cations, Divalent; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D008274:Magnesium; D002118:Calcium