Why is magnesium an NMDA antagonist?

[mycotheology]

The NMDA receptor is a ligand gated non selective cation channel. It allows Na⁺ and to a lesser extent Ca²⁺ and K⁺ to pass through. I read that Mg²⁺ clogs up the pore. Why would Mg2+ block the channel but not Ca²⁺? Ca²⁺ is larger so I'd expect that to be more likely to block an ion channel. Is it because Mg²⁺ is more electronegative than Ca²⁺?

 

[chill_factor]

The NMDA receptor is a ligand gated non selective cation channel. It allows Na⁺ and to a lesser extent Ca²⁺ and K⁺ to pass through. I read that Mg²⁺ clogs up the pore. Why would Mg2+ block the channel but not Ca²⁺? Ca²⁺ is larger so I'd expect that to be more likely to block an ion channel. Is it because Mg²⁺ is more electronegative than Ca²⁺?

I'd say its because Mg2+ is the smallest charge 2 ion and is more reactive than Ca2+; clogging up the pore might just mean that it deactivates the protein, not actually block the pore, right? Just my opinion, I'm no expert.

 

[mycotheology]

Heres a quote from an abstract:

Physiological concentrations of magnesium reduce responses to N M D A by blocking the NMDA-associated ionophore in a voltage-dependent manner [2].

deepblue.lib.umich.edu/bitstream/2027.42/28723/1/0000544.pdf

In a voltage dependent manner so what you said must be correct. Magnesiums size-charge ratio is behind it. I read something about NMDA receptors being partially voltage gated.