INTRACELLULAR POLYAMINES MEDIATE INWARD RECTIFICATION OF CA2-PERMEABLE LPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID RECEPTORS()

lpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) recepto rs that lack the glutamate receptor GluR2 subunit are Ca2+-permeable a nd exhibit inwardly rectifying current responses to kainate and AMPA. A proportion of cultured rat hippocampal neurons show similar Ca2+-per meable inwardly rectifying AMPA receptor currents. Inward rectificatio n in these neurons was lost with intracellular dialysis and was not pr esent in excised outside-out patches but was maintained in perforated- patch whole-cell recordings, suggesting that a diffusible cytoplasmic factor may be responsible for rectification. Inclusion of the naturall y occurring polyamines spermine and spermidine in the recording pipett e prevented loss of rectification in both whole-cell and excised-patch recordings; Mg2+ and putrescine were without effect. Inward rectifica tion of Ca2+-permeable AMPA receptors may reflect voltage-dependent ch annel block by intracellular polyamines.