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

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作者：

M Hollmann，J Boulter，C Maron，L Beasley，J Sullivan，G Pecht，S Heinemann

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摘要：

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.

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CiteSeerX citations Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor M Hollman J Boulter C Maron L Beasley J Sullivan G Pecht S Heinemann