The polyamine spermine has multiple actions on N-methyl-D-aspartate receptor single-channel currents in cultured cortical neurons.

Spermine potentiates the action of N-methyl-D-aspartate (NMDA) at micromolar concentrations but is less effective at millimolar concentrations. In cultured cortical neurons we demonstrate that spermine enhances NMDA receptor currents in a unique manner. At low concentrations (1-10 microM) spermine enhances NMDA receptor current by increasing channel opening frequency, and at higher concentrations (greater than 10 microM) it produces, in addition, a voltage-dependent decrease in channel amplitude and average open time that limits its enhancing action. It is likely that these two actions of spermine, due to differences in concentration and voltage dependence, are mediated by independent sites on the NMDA receptor complex.