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

doi:10.1186/s13041-018-0406-3

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 journal › Article › peer-review

23 Citations (Scopus)

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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 (PrP^C), and that PrP^C regulation of NMDA receptors is copper-dependent. Here, we employed electrophysiological methods to study NMDAR and AMPAR currents of cultured hippocampal neurons from PrP^C overexpresser mice. We show that NMDA receptor current amplitude and kinetics are differentially modulated by overexpression of human or mouse PrP^C. 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 PrP^C, but share common modulation by copper ions.

Original language	English
Article number	62
Pages (from-to)	1-6
Number of pages	6
Journal	Molecular Brain
Volume	11
Issue number	1
DOIs	https://doi.org/10.1186/s13041-018-0406-3
Publication status	Published - 25 Oct 2018
Externally published	Yes

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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10.1186/s13041-018-0406-3

Publisher version (open access)Final published version, 1.12 MBLicence: CC BY

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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.",

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AU - Bladen, Chris

AU - Stys, Peter K.

AU - Zamponi, Gerald W.

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

Abstract

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