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Functional plasticity of the N-methyl-D-aspartate receptor in differentiating human erythroid precursor cells

Lookup NU author(s): Dr Seva TelezhkinORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Calcium signaling is essential to support erythroid proliferation and differentiation. Precise control of the intracellular Ca2+ levels in erythroid precursor cells (EPCs) is afforded by coordinated expression and function of several cation channels, including the recently identified N-methyl-d-aspartate receptor (NMDAR). Here, we characterized the changes in Ca2+ uptake and electric currents mediated by the NMDARs occurring during EPC differentiation using flow cytometry and patch clamp. During erythropoietic maturation, subunit composition and properties of the receptor changed; in proerythroblasts and basophilic erythroblasts, fast deactivating currents with high amplitudes were mediated by the GluN2A subunit-dominated receptors, while at the polychromatic and orthochromatic erythroblast stages, the GluN2C subunit was getting more abundant, overriding the expression of GluN2A. At these stages, the currents mediated by the NMDARs carried the features characteristic of the GluN2C-containing receptors, such as prolonged decay time and lower conductance. Kinetics of this switch in NMDAR properties and abundance varied markedly from donor to donor. Despite this variability, NMDARs were essential for survival of EPCs in any subject tested. Our findings indicate that NMDARs have a dual role during erythropoiesis, supporting survival of polychromatic erythroblasts and contributing to the Ca2+ homeostasis from the orthochromatic erythroblast stage to circulating red blood cells.

Publication metadata

Author(s): Hänggi P, Telezhkin V, Kemp PJ, Schmugge M, Gassmann M, Goede JS, Speer O, Bogdanova A

Publication type: Article

Publication status: Published

Journal: American Journal of Physiology: Cell Physiology

Year: 2015

Volume: 308

Issue: 12

Pages: C993–C1007

Print publication date: 15/06/2015

Acceptance date: 17/03/2015

Date deposited: 09/03/2017

ISSN (print): 0363-6143

ISSN (electronic): 1522-1563

Publisher: American Physiological Society


DOI: 10.1152/ajpcell.00395.2014

PubMed id: 25788577


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