PMID- 28459106
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240313
IS  - 2398-502X (Print)
IS  - 2398-502X (Electronic)
IS  - 2398-502X (Linking)
VI  - 2
DP  - 2017 Mar 17
TI  - Functional assessment of the NMDA receptor variant GluN2A (R586K).
PG  - 20
LID - 10.12688/wellcomeopenres.10985.2 [doi]
LID - 20
AB  - Background: The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate 
      receptor that has important roles in synaptogenesis, synaptic transmission, and 
      synaptic plasticity. Recently, a large number of rare genetic variants have been 
      found in NMDAR subunits in people with neurodevelopmental disorders, and also in 
      healthy individuals. One such is the GluN2A(R586K) variant, found in a person 
      with intellectual disability. Identifying the functional consequences, if any, of 
      such variants allows their potential contribution to pathogenesis to be assessed. 
      Here, we assessed the effect of the GluN2A(R586K) variant on NMDAR pore 
      properties. Methods: We expressed recombinant NMDARs with and without the 
      GluN2A(R586K) variant in Xenopus laevis oocytes and in primary cultured mouse 
      neurons, and made electrophysiological recordings assessing Mg(2+) block, 
      single-channel conductance, mean open time and current density. Results: The 
      GluN2A(R586K) variant was not found to influence any of the properties assessed. 
      Conclusions: Our findings suggest it is unlikely that the GluN2A(R586K) variant 
      contributes to the pathogenesis of neurodevelopmental disorder.
FAU - Marwick, Katie F M
AU  - Marwick KFM
AUID- ORCID: 0000-0003-1753-4626
AD  - Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, 
      UK.
FAU - Parker, Peter
AU  - Parker P
AD  - Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, 
      UK.
FAU - Skehel, Paul
AU  - Skehel P
AD  - Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, 
      UK.
FAU - Hardingham, Giles
AU  - Hardingham G
AD  - Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, 
      UK.
FAU - Wyllie, David J A
AU  - Wyllie DJA
AUID- ORCID: 0000-0002-4957-6049
AD  - Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, 
      UK.
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - 102838/Wellcome Trust/United Kingdom
GR  - G0902044/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20170317
PL  - England
TA  - Wellcome Open Res
JT  - Wellcome open research
JID - 101696457
PMC - PMC5407442
MID - EMS72386
OTO - NOTNLM
OT  - EEG
OT  - NMDAR
OT  - conductance
OT  - electrophysiology
OT  - epilepsy
OT  - intellectual disability
OT  - magnesium
OT  - neurons
COIS- Competing interests: No competing interests were disclosed.
EDAT- 2017/05/02 06:00
MHDA- 2017/05/02 06:01
PMCR- 2017/04/26
CRDT- 2017/05/02 06:00
PHST- 2017/05/02 06:00 [entrez]
PHST- 2017/05/02 06:00 [pubmed]
PHST- 2017/05/02 06:01 [medline]
PHST- 2017/04/26 00:00 [pmc-release]
AID - 10.12688/wellcomeopenres.10985.2 [doi]
PST - epublish
SO  - Wellcome Open Res. 2017 Mar 17;2:20. doi: 10.12688/wellcomeopenres.10985.2.