TY - JOUR T1 - Identification of Domains and Amino Acids Involved in GluR7 Ion Channel Function JF - The Journal of Neuroscience JO - J. Neurosci. SP - 401 LP - 411 DO - 10.1523/JNEUROSCI.21-02-00401.2001 VL - 21 IS - 2 AU - Nathalie Strutz AU - Carmen Villmann AU - Agnes Thalhammer AU - Pablo Kizelsztein AU - Miriam Eisenstein AU - Vivian I. Teichberg AU - Michael Hollmann Y1 - 2001/01/15 UR - http://www.jneurosci.org/content/21/2/401.abstract N2 - The kainate receptors GluR6 and GluR7 differ considerably in their ion channel properties, despite sharing 86% amino acid sequence identity. When expressed in Xenopus oocytes GluR6 conducts large agonist-evoked currents, whereas GluR7 lacks measurable currents. In the present study, we localized the determinants that are responsible for the functional differences between GluR6 and GluR7 to the extracellular loop domain L3. In addition, we generated several GluR7 point mutants that are able to conduct currents that can be readily measured in Xenopus oocytes.In GluR6, glutamate- and kainate-evoked maximal currents are of the same magnitude when desensitization is inhibited with the lectin concanavalin A. By contrast, all functional GluR7 mutants were found to have glutamate current amplitudes significantly larger than those evoked by kainate. We localized the domain that determines the relative agonist efficacies to the C-terminal half of the L3 domain of GluR7.Our data show that EC50 values for glutamate (but not for kainate) in GluR7 mutants or chimeras tend to be increased in comparison to the EC50 values in GluR6. The high EC50 for wild-type GluR7 reported in the literature appears to be linked to the S1 portion of the agonist-binding domain.Finally, we determined the C-terminal half of the L3 domain plus the far C-terminal domain of GluR7 to be responsible for the recently reported reduction of current amplitude seen when GluR7 is coexpressed with GluR6. We conclude that coexpression of GluR6 and GluR7 leads to nonstochastical assembly of heteromeric receptor complexes. ER -