Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor

Neuron. 1993 May;10(5):943-54. doi: 10.1016/0896-6273(93)90209-a.


We have determined the gene structure for the NMDA receptor subunit gene NMDAR1. We found eight splice variants that arise from different combinations of a single 5' terminal exon insertion and three different 3' terminal exon deletions, relative to NMDAR1. We analyzed the modulation by Zn2+ of currents through homomeric receptors assembled from these splice variants and found that, in addition to its well-known inhibitory effect at high concentrations, Zn2+ potentiates agonist-induced currents at submicromolar concentrations (EC50 = 0.50 microM). This potentiation is observed only with a subset of NMDAR1 splice variants that show additional differences in pharmacological properties. Zn2+ potentiation is rapidly reversible, noncompetitive with either glutamate or glycine, and voltage independent. Zn2+ potentiation is mimicked by Cd2+, Cu2+, and Ni2+, but not by Mn2+, Co2+, Fe3+, Sn2+, or Hg2+. Our results suggest a possible role for Zn2+ as a positive modulator of NMDA receptors in certain regions of the brain.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cations
  • DNA / chemistry
  • Drug Synergism
  • Electric Conductivity
  • Exons
  • Gene Deletion
  • Gene Expression
  • Genetic Variation
  • Introns
  • Molecular Sequence Data
  • Oocytes / metabolism
  • RNA / genetics
  • RNA Splicing*
  • RNA, Complementary
  • Rats
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Transfection
  • Xenopus
  • Zinc / pharmacology*


  • Cations
  • RNA, Complementary
  • Receptors, N-Methyl-D-Aspartate
  • RNA
  • DNA
  • Zinc

Associated data

  • GENBANK/L08228