Closure of the ligand-binding domain (LBD) of glutamate receptor channels opens their gate by a mechanism that is not fully clear. We find that glycine substitutions of pore facing residues in the conserved SYTANLAAF region in the transmembrane M3 helix of GluA2 improve gating. notably, replacing alanine 621 with glycine, two turns of the helix below the gate, resulted in a non-desensitizing channel with significant agonist-independent basal activity and ∼ 36-fold increase in glutamate potency without changes in expression or binding. On GluA2(A621G), the partial agonist kainate acted as a full agonist and the antagonist CNQX acted as a partial agonist. In contrast, a glycine mutation above the channel gate, reduced activity and glutamate potency. Therefore, closure of the LBD opens the channel by pulling apart the M3 helix around a pivot at small flexible amino acids in the pore facing region below the gate, in a mechanism similar to potassium channel gating.