Glutamate receptor ionotropic, NMDA 2A

Definition:

Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have lower sensitivity to glutamate and faster deactivation kinetics than channels formed by GRIN1 and GRIN2B. Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity).

References:

[1]. S D Hess, et al. Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors. J Pharmacol Exp Ther. 1996 Aug;278(2):808-16. [Content Brief]

[2]. David H Hackos, et al. Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function. Neuron. 2016 Mar 2;89(5):983-99. [Content Brief]

[3]. Elisia Villemure, et al. GluN2A-Selective Pyridopyrimidinone Series of NMDAR Positive Allosteric Modulators with an Improved in Vivo Profile. ACS Med Chem Lett. 2016 Oct 31;8(1):84-89. [Content Brief]

[4]. Matthew Volgraf, et al. Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators (PAMs): Tuning Deactivation Kinetics via Structure-Based Design. J Med Chem. 2016 Mar 24;59(6):2760-79. [Content Brief]

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