NMDA Excitotoxicity, Vitamin D, Magnesium And Copper

Kingpinguin

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Got interested in neruonal cell death through NMDA activation. I think most people know magnesium is needed to block, calm down NMDA over activation. N-methyl D-aspartic acid itself is a neurotoxin. Reason why I became interested is because of people having so much problem with high dose vitamin D. The fact that vitamin D depletes magnesium and that vitamin D also is an NMDA agonist makes me believe that this agonism it has is the reason why over-supplementation or vitamin D tends to give people insomnia, anxiety and panic attacks. High enough doses has been shown to induce seizures and coma in some cases. And there’s many reports that magnesium helps counter vitamin D toxicity symptoms. Makes sense since magnesium is an NMDA antagonist. And its likely that vit Ds toxic effects is from NMDA agonism and that vitamin D in high enough doses or just having too high calcium could cause neuronal cell death through NMDA-receptor What did suprise me tho is that another mineral copper is needed to desensetize and sensetize the NMDA receptors from excess currents and excitability. This goes to show the importance of copper and another way its beneficial for neurological disease.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382327/


- ”Given the ability of copper to potently modulate NMDA receptor kinetics and limit agonist-induced inward current and therefore Ca2+ loads (see above), it is plausible that ambient copper in culture media and brain extracellular space functions to limit NMDA receptor-dependent excitotoxicity. In line with this prediction, treatment of cultured neurons with copper chelators causes cell death that can be prevented by the NMDA receptor antagonist 5,7-dichlorokynurenic acid or by supplying excess copper (You et al. 2012).”

- ”We would therefore argue that copper ions might have to be supplied exogenously to maintain consistent concentrations, similar to what is done routinely with magnesium.”

- ”It should be noted that copper ions not only modulate NMDA receptors, but also a variety of other types of ion channels. For example, AMPA receptors in rat cortical neurons are blocked with IC50 values of around 5 μm, and at saturating levels of copper (i.e. 30 μm) agonist affinity for these receptors is reduced (Weiser & Wienrich, 1996). Copper ions also block T-type calcium channels and high voltage activated calcium channels with affinities ranging from ∼1 to 30 μm depending on calcium channel subtype (Jeong et al. 2003; Lu et al.2009), and they modulate ENaC channels in the submicromolar range (Lu et al. 2009).”

at wiki under NMDA receptor antagonist I also found this study about copper.

[PDF] Zinc and copper influence excitability of rat olfactory bulb neurons by multiple mechanisms. | Semantic Scholar

- ”However, in contrast to the similarity of their effects on inhibitory transmission, spontaneous glutamate-mediated excitatory synaptic activity was completely blocked by copper but only inhibited by zinc.”
 
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