Unblocking of NMDA receptors, glutamate binding and activation

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R-HSA-438066
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Pathway
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Homo sapiens
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At resting membrane potential, the NMDA receptor ion channel is blocked by extracellular Mg2+ ions and is unable to mediate ion permeation upon binding of ligands (glutamate, glycine, D-serine, NMDA). The voltage block is removed upon depolarization of the post-synaptic cell membrane and Mg2+ is expelled from the NMDA receptor pore (channel), resulting in activated ligand-bound NMDA receptors. The depolarization of the membrane may happen in response to activation of Ca2+ impermeable AMPA receptors, which facilitates Na+ influx, contributing to the unblocking of NMDA receptors. For review, please refer to Traynelis et al. 2010, Paoletti et al. 2013, and Iacobucci and Popescu 2017.

Literature References
PubMed ID Title Journal Year
20716669 Glutamate receptor ion channels: structure, regulation, and function

Traynelis, SF, Wollmuth, LP, McBain, CJ, Menniti, FS, Vance, KM, Ogden, KK, Hansen, KB, Yuan, H, Myers, SJ, Dingledine, R

Pharmacol. Rev. 2010
28303017 NMDA receptors: linking physiological output to biophysical operation

Iacobucci, GJ, Popescu, GK

Nat. Rev. Neurosci. 2017
23686171 NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease

Paoletti, P, Bellone, C, Zhou, Q

Nat. Rev. Neurosci. 2013
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