Functional assessment of the NMDA receptor variant GluN2A R586K

Wellcome Open Research

article

Katie F.M. Marwick¹  Peter Parker¹  Paul Skehel¹  Giles Hardingham¹  David J.A. Wyllie¹ 

[1] Centre for Integrative Physiology, University of Edinburgh

关键词: NMDAR;    epilepsy;    EEG;    intellectual disability;    electrophysiology;    magnesium;    conductance;    neurons;   

DOI  :  10.12688/wellcomeopenres.10985.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

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 GluN2AR586K variant (GRIN2AG1757A), 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 GluN2AR586K variant on NMDAR pore properties.Methods: We expressed recombinant NMDARs with and without the GluN2AR586K variant inXenopus laevis oocytes and in primary cultured mouse neurons, and made electrophysiological recordings assessing Mg2+ block, single-channel conductance, mean open time and current density.Results: The GluN2AR586K variant was not found to influence any of the properties assessed.Conclusions: Our findings suggest it is unlikely that the GluN2AR586K variant contributes to the pathogenesis of neurodevelopmental disorder.

【 授权许可】

CC BY