Drucken

M. Hollmann, J. Boulter, C. Maron, L. Beasley, J. Sullivan, G. Pecht, and S. Heinemann (1993).
Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor.
Neuron 10(5): 943-954.
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 µM). This potentiation is observed only with a subset of NMDAR1 splice variants that show additional differences in pharmacological properties. Zn2+ potentiation is rapidly reversible, non-competitive with either glutamate or glycine, and voltage independent. Zn²⁺ potentiation is mimicked by Cd²⁺, Cu²⁺, and Ni²⁺, but not by Mn²⁺, Co²⁺, Fe²⁺, Sn²⁺, or Hg²⁺. Our results suggest a possible role for Zn²⁺ as a positive modulator of NMDA receptors in certain regions of the brain.