Differential modulation of NMDA and AMPA receptors by cellular prion protein and copper ions

Sun Huang, Lina Chen, Chris Bladen, Peter K. Stys, Gerald W. Zamponi*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)
5 Downloads (Pure)

Abstract

N-Methyl-D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are two major types of ionotropic glutamate receptors involved in synaptic transmission. However, excessive activity of these receptors can be cytotoxic and thus their function must be precisely controlled. We have previously reported that NMDA receptor activity is dysregulated following genetic knockout of cellular prion protein (PrPC), and that PrPC regulation of NMDA receptors is copper-dependent. Here, we employed electrophysiological methods to study NMDAR and AMPAR currents of cultured hippocampal neurons from PrPC overexpresser mice. We show that NMDA receptor current amplitude and kinetics are differentially modulated by overexpression of human or mouse PrPC. By contrast, AMPA receptor activity was unaffected. Nonetheless, AMPA receptor activity was modulated by copper ions in a manner similar to what we previously reported for NMDA receptors. Taken together, our findings reveal that AMPA and NMDA receptors are differentially regulated by PrPC, but share common modulation by copper ions.

Original languageEnglish
Article number62
Pages (from-to)1-6
Number of pages6
JournalMolecular Brain
Volume11
Issue number1
DOIs
Publication statusPublished - 25 Oct 2018
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • AMPA receptor
  • Cellular prion protein
  • CNS disorders
  • Copper
  • Hippocampal neurons
  • Knock-in mice
  • NMDA receptor
  • Whole-cell patch clamp

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