Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block

AbstractCa2+-permeable glutamate receptors assembled from subunits containing a GLN residue at the RNA editing site in membrane domain 2 show strong inward rectification. In HEK 293 cells transfected with the kainate receptor subunit GIuR6(Q), inward rectification is lost in outside-out patches, suggesting a role for diffusible, cytoplasmic factors. Inclusion of different polyamines in the internal solution restored inward rectification, whereas Mg2+ (1 mM) was inactive. Spermine (Kd[0 mV] = 5.5 μM) was of higher affinity than spermidine (Kd[0 mV] = 25.4 μM) or putrescine (Kd[0 mV] = 1.2 mM). AMPA receptors assembled from GIuRAflip showed even higher affinity for spermine (Kd[0 mV] = 1.5 μM). Analysis of the voltage dependence of whole-cell responses predicted intracellular free spermine and spermidine concentrations of 51 and 153 μM, respectively