A single amino acid residue determines the Ca²⁺ permeability of AMPA-selective glutamate receptor channels

Functional analysis of AMPA-selective glutamate receptor channels expressed in Xenopus oocytes from cloned cDNAs has shown that homomeric channels formed by the G1uR1 subunit are permeable to Ca²⁺, whereas heteromeric channels composed of the GluR1 and G1uR2 subunits show little permeability. Furthermore, substitution of glutamine for arginine in putative transmembrane segment M2 of the GluR2 subunit makes the heteromeric channels permeable to Ca²⁺. These results suggest that the G1uR2 subunit plays a key role in keeping AMPAselective glutamate receptor channels essentially impermeable to Ca²⁺ and that the critical determinant is the positively charged residue in M2 segment.