Abstract
A single site in recombinant glutamate receptor channels of the GluR1-GluR4 family has been previously identified as a key regulator of ion permeation. The natural amino acid at this position (arginine in GluR2 but glutamine in GluR1, GluR3, and GluR4) determines both the ability to pass outward current and the divalent cation permeability of kainate-activated receptor channels. By mutagenesis of GluR6, we demonstrated that the same site also controls the ability to pass outward current in another non-NMDA receptor family. Additional mutations at and near this site in GluR3 indicated that the position of the arginine is critical to function, that the ability to pass outward current is not necessarily linked to low barium permeability, and that the size as well as the charge of the side chain at this position influences barium permeation. These results provide evidence that this site forms part of the selectivity filter of glutamate receptor channels.