Residues at the tip of the pore loop of NR3B-containing NMDA receptors determine Ca<Superscript>2+</Superscript> permeability and Mg<Superscript>2+</Superscript>block

Background  

Members of the complex N-methyl-D-aspartate receptor (NMDAR) subfamily of ionotropic glutamate receptors (iGluRs) conventionally assemble from NR1 and NR2 subunits, the composition of which determines receptor properties. Hallmark features of conventional NMDARs include the requirement for a coagonist, voltage-dependent block by Mg²⁺, and high permeability for Ca²⁺. Both Mg²⁺ sensitivity and Ca²⁺ permeability are critically dependent on the amino acids at the N and N+1 positions of NR1 and NR2. The recently discovered NR3 subunits feature an unprecedented glycine-arginine combination at those critical sites within the pore. Diheteromers assembled from NR1 and NR3 are not blocked by Mg²⁺ and are not permeable for Ca²⁺.