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Mol Brain. 2018 Oct 25;11(1):62. doi: 10.1186/s13041-018-0406-3.

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

Huang S1,2,3, Chen L1,2,3, Bladen C1,2,3, Stys PK4,2, Zamponi GW5,6,7.

Author information

1
Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
2
Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
3
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
4
Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
5
Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada. zamponi@ucalgary.ca.
6
Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. zamponi@ucalgary.ca.
7
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada. zamponi@ucalgary.ca.

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.

KEYWORDS:

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

PMID:
30359282
PMCID:
PMC6202830
DOI:
10.1186/s13041-018-0406-3
[Indexed for MEDLINE]
Free PMC Article

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