NMDA receptor
Jump to navigation
Jump to search
Function
- excitatory voltage-gated glutamate receptor/ion channel
- transiently activated by nM concentrations of glutamate following depolarization of the postsynaptic membrane
- depolarization attenuates voltage-dependent Mg+2 block of NMDA receptors
- activity of the NMDA receptor is associated with long-term potentiation (LTP) & long-term depression (LTD) in the hippocampus[6][9][10]
- LTP is dependent upon the NR2A subunit & LTD on the NR2B subunit
- the NMDA receptor requires both glutamate & glycine for efficient gating
- D-serine is a coagonist with glutamate at NMDA receptors[11]
- Mg+2 blocks the NMDA receptor in a voltage-dependent manner, but potentiates NMDA-responses at positive membrane potentials
- Na+, K+ & Ca+2 pass through the NMDA receptor channel & modulate the activity the receptor
- Zn+2 blocks the NMDA current in a noncompetitive & voltage-independent manner
- polyamines modulate glutamate-mediated responses
- activity of NMDA receptors is sensitive to H+ ions
- oxidation of a redox-modulated site inactivates the NMDA receptor.
- tyrosine phosphorylation by src family proteins increases activity of the NMDA receptor
Structure
- forms heteromeric channel of:
- zeta subunit (GRIN1)
- epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D)
- third subunit (GRIN3A or GRIN3B)
Compartment
- excitatory glutamate receptors in the CNS are predominantly dendritic[5], embedded within the postsynaptic density
Expression
- present throughout the brain & spinal cord
- consistently present in excitatory synapses of the forebrain
Pathology
- anti-NMDA receptor antibodies associated with anti-NMDA receptor encephalitis
Pharmacology
- memantine (Namenda) is a low-moderate affinity NMDA receptor antagonist FDA approved in 2003 for moderate to advanced Alzheimer's disease.
More general terms
Additional terms
- anti-NMDA receptor encephalitis; NMDAR Ab encephalitis
- long term potentiation (LTP)
- memantine (Auzura, Namenda, Exiba, Akatinol)
- NMDA receptor antagonist
- NMDA receptor-regulated protein 1; N-alpha-acetyltransferase 15, natA auxiliary subunit; gastric cancer antigen Ga19; N-terminal acetyltransferase; protein tubedown-1; Tbdn100 (NAA15, GA19, NARG1, NATH, TBDN100)
References
- ↑ Choi 1988
- ↑ Aizenman E, Hartnett KA, Reynolds IJ. Oxygen free radicals regulate NMDA receptor function via a redox modulatory site. Neuron. 1990 Dec;5(6):841-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2148489
- ↑ Ben-Ari Y, Aniksztejn L, Bregestovski P. Protein kinase C modulation of NMDA currents: an important link for LTP induction. Trends Neurosci. 1992 Sep;15(9):333-9. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1382331
- ↑ Barnard EA. Receptor classes and the transmitter-gated ion channels. Trends Biochem Sci. 1992 Oct;17(10):368-74. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1360717
- ↑ 5.0 5.1 Ikegaya Y, Kim JA, Baba M, Iwatsubo T, Nishiyama N, Matsuki N. Rapid and reversible changes in dendrite morphology and synaptic efficacy following NMDA receptor activation: implication for a cellular defense against excitotoxicity. J Cell Sci. 2001 Nov;114(Pt 22):4083-93. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11739640
- ↑ 6.0 6.1 Villarreal DM, Do V, Haddad E, Derrick BE. NMDA receptor antagonists sustain LTP and spatial memory: active processes mediate LTP decay. Nat Neurosci. 2002 Jan;5(1):48-52. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11740500
- ↑ Sheng M. Molecular organization of the postsynaptic specialization. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7058-61. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11416187
- ↑ Yaka R, Thornton C, Vagts AJ, Phamluong K, Bonci A, Ron D. NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5710-5. Epub 2002 Apr 9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11943848
- ↑ 9.0 9.1 Liu L, Wong TP, Pozza MF, Lingenhoehl K, Wang Y, Sheng M, Auberson YP, Wang YT. Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity. Science. 2004 May 14;304(5673):1021-4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15143284
- ↑ 10.0 10.1 Bliss T, Schoepfer R. NEUROSCIENCE: Controlling the Ups and Downs of Synaptic Strength. Science. 2004 May 14;304(5673):973-4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15143268
- ↑ 11.0 11.1 UniProt http://www.uniprot.org/uniprot/Q9GZT4.html
- ↑ Wikipedia; Note: NMDA receptor entry http://en.wikipedia.org/wiki/NMDA_receptor
- ↑ Dalmau J, Gleichman AJ, Hughes EG et al Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008 Dec;7(12):1091-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18851928