Spermine blocks synaptic transmission mediated by Ca(2+)-permeable AMPA receptors

AMPA-gated glutamate receptors with outward rectification (type I receptors) are almost impermeable to Ca2+, while those with strong inward rectification (type II receptors) have high Ca2+ permeability. In the present study current responses in rat hippocampal neurones mediated by type II AMPA receptors were blocked by application of spermine to the external solution (IC50 = 170 microM), but those mediated by type I AMPA receptors were not affected. Furthermore, in putative non-pyramidal neurones in rat hippocampal slices, EPSCs mediated by type II AMPA receptors were markedly reduced by 1mM spermine, while those mediated by type I AMPA receptors were much less affected. Thus, external spermine exerts differential blocking action on the two different types of AMPA receptors.