The endogenous polyamines, spermine, spermidine, and putrescine have effects on several types of cation channels. Intracellular polyamines, in particular spermine, contribute to intrinsic gating and rectification of strong inward rectifier K+ channels. Intracellular spermine is also responsible for inward rectification of some types of Ca(2+)-permeable AMPA and kainate receptors. Spermine has a number of effects on the activity of the NMDA subtype of glutamate receptor, involving two or more extracellular polyamine binding sites on the NMDA receptor. In K+ channels and glutamate receptors, some of the amino acids in the receptor/channel structure that influence to polyamines have been identified, leading to a partial understanding of the effects of polyamines at a molecular level. Block of K+ channels by intracellular polyamines is likely to be an important receptors by intracellular spermine and modulation by extracellular spermine may affect excitability and the influx of Ca2+ in neurons and glial cells of the nervous system.