Investigation via ion pore transplantation of the putative relationship between glutamate receptors and K+ channels

The pore domains of ionotropic glutamate receptors (iGluRs) and potassium channels (K+ channels) show several structural similarities. To test for functional compatibility, we transferred pore regions from prokaryotic, invertebrate, and vertebrate K+ channels into pharmacologically representative iGluRs and vice versa. Although the chimeric proteins were expressed on the cell surface, only one of 45 pore chimeras showed ion channel function: The kainate receptor subunit GluR6, carrying the pore loop plus adjacent transmembrane domains of the prokaryotic, glutamate-gated, K+-selective GluR0, adopted several electrophysiological properties of the donor pore upon pore transplantation. This suggests that, despite structural similarities between iGluR and K+ channel pores, there is a lack of functional compatibility so that K+ channel pores cannot be gated by the iGluR gating machinery, and vice versa. However, K+-selective pores can be gated in an iGluR sequence environment, given a similar signal transduction mechanism as appears to be present in GluR0.