Fig. 4: GluE1αA mutations that alter ligand specificity also affect pharmacological sensitivity to CNQX and AMPA.

a Sample whole-cell recordings demonstrating that GluE1αA is not sensitive to 1 mM AMPA, kainate, NMDA, or quisqualate, while the m3 variant is sensitive to AMPA. b Bar plot of average normalized peak inward currents of wt, m2, and m3 variants of GluE1αA in response to different agonists at 1 mM (n = 6–7). Letters above the bars denote statistically significant differences for applied compounds based on post hoc Tukey tests (p < 1E−4) after One Way ANOVAs (glycine: F = 809.23, p = 5.55E−16; glutamate: F = 367.97, p = 1.79E−13; AMPA: F = 126.50, p = 4.07E−10). Specifically, means/bars with the same letters above them are not statistically different, while those with different letters are different based on Tukey tests. c Sample continuous GluE1αA wt and m3 currents elicited by 1 second perfusion of 10 mM glycine or glutamate with increasing concentrations of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; applied 2 seconds prior to ligands and during ligand application). The legend at the bottom indicates the duration of perfusion of glycine or glutamate ligands and CNQX. d CNQX dose response curves for the wildtype and m3 variants of GluE1αA normalized to peak current amplitude in the absence of CNQX (n = 6-9). IC₅₀ values for the wildtype receptor, derived using a standard monophasic dose response function, and IC₅₀ and EC₅₀ values for the m3 variant, derived using a biphasic dose response function⁸⁷, are indicated. The p-values indicated in cyan text are for two sample T-tests comparing normalized mean current amplitude of the GluE1αA m3 variant in the absence of CNQX vs. 1 µM CNQX, and of the mean IC₅₀ values of wildtype GluE1αA vs. the m3 variant.