Reactome | Unblocking of NMDA receptors, glutamate binding and activation

Unblocking of NMDA receptors, glutamate binding and activation

Stable Identifier

R-HSA-438066

Type

Pathway

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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Unblocking of NMDA receptors, glutamate binding and activation

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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
28303017	NMDA receptors: linking physiological output to biophysical operation Iacobucci, GJ, Popescu, GK	Nat. Rev. Neurosci.	2017
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
23686171	NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease Paoletti, P, Bellone, C, Zhou, Q	Nat. Rev. Neurosci.	2013