The GluN3 subunit regulates ion selectivity within native N-methyl-d-aspartate receptors.

•The GluN3 subunit is the least understood of all subunits that make up functional NMDARs in the brain.•We show through ion substitution experiments that NMDARs containing GluN3 are more permeable to Ca2+ than those containing just GluN1 and GluN2.•We attribute these differences to their ability to screen for Ca2+ over Na+.•Subunit-dependent cation selectivity represents a hitherto unrealized mechanism for finer control of Ca2+ influx enhancing the repertoire of synaptic NMDARs.