Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit

Functionally diverse GIuR channels of the AMPA subtype are generated by the assembly of GIuR-A, -B, -C, and -D subunits into homo- and heteromeric channels. The GIuR-B subunit is dominant in determining functional properties of heteromeric AMPA receptors. This subunit exists in developmentally distinct edited and unedited forms, GIuR-B(R) and GIuR-B(Q), which differ in a single amino acid in transmembrane segment TM2 (Q/R site). Homomeric GIuR-B(R) channels expressed in 293 cells display a low divalent permeability, whereas homomeric GluR-B(Q) and GIuR-D channels exhibit a high divalent permeability. Mutational analysis revealed that both the positive charge and the size of the amino acid side chain located at the Q/R site control the divalent permeability of homomeric channels. Coexpression of Q/R site arginine- and glutamine-containing subunits generates cells with varying divalent permeabilities depending on the amounts of expression vectors used for cell transfection. Intermediate divalent permeabilities were traced to the presence of both divalent permeant homomeric and impermeant heteromeric channels. It is suggested that the positive charge contributed by the arginine of the edited GIuR-B(R) subunit determines low divalent permeability in heteromeric GIuR channels and that changes in GIuR-B(R) expression regulate the AMPA receptor-dependent divalent permeability of a cell.