INWARD RECTIFICATION OF BOTH AMPA AND KAINATE SUBTYPE GLUTAMATE RECEPTORS GENERATED BY POLYAMINE-MEDIATED ION-CHANNEL BLOCK

Ca2+-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 GluR6(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 (K-d[0 mV] = 5.5 mu M) was of higher affinity than spermidine (K-d[0 mV] = 25.4 mu M) or putrescine (K-d[0 mV] = 1.2 mM). AMPA receptors assembled from GluR(flip), showed even higher affinity for spermine (K-d[0 mV] = 1.5 mu M) Analysis of the voltage dependence of whole-cell responses predicted intracellular free spermine and spermidine concentrations of 51 and 153 mu M, respectively.