Identification of a high affinity divalent cation binding site near the entrance of the NMDA receptor channel

Neuron. 1996 Apr;16(4):869-80. doi: 10.1016/s0896-6273(00)80107-5.


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+.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Cations, Divalent
  • Electric Conductivity
  • Female
  • Kinetics
  • Magnesium / metabolism*
  • Magnesium / pharmacology
  • Membrane Potentials
  • Mice
  • Mutagenesis
  • Oocytes
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Thermodynamics
  • Xenopus laevis


  • Cations, Divalent
  • Receptors, N-Methyl-D-Aspartate
  • Recombinant Proteins
  • Magnesium
  • Calcium