POLYAMINE REGULATION OF N-METHYL-D-ASPARTATE RECEPTOR CHANNELS

Endogenous polyamines such as spermine and spermidine have multiple ef fects in the central nervous system and have been suggested to be neur otransmitters or neuromodulators. One effect of the polyamines is to r egulate the activity of the N-methyl-D-aspartate receptor (NMDAR) chan nel subtype of glutamate receptor channels. The effects of polyamines on NMDAR currents are complex, suggesting the presence of one or more polyamine-binding sites on the receptor channel. Electrophysiological studies have shown that polyamines enhance NMDAR currents by increasin g channel opening frequency and by increasing the affinity of the rece ptor for glycine. Polyamines have been shown to reduce NMDAR currents by producing voltage-dependent reduction of single-channel amplitudes and/or by producing an open channel block. Recent molecular biological studies have shown that the polyamine effects on NMDAR channels invol ve interactions with multiple NMDAR subunits and are characterizing th e structural basis for the polyamine regulation of NMDAT receptor chan nels.