Sensitivity of the N-methyl-D-aspartate receptor to polyamines is controlled by NR2 subunits.

摘要: The endogenous polyamine spermine has multiple effects on the N-methyl-D-aspartate (NMDA) receptor. These include an increase in magnitude of NMDA-induced whole-cell currents that is seen presence saturating concentrations glycine ("glycine-independent" stimulation), affinity receptor for ("glycine-dependent" and voltage-dependent inhibition. Although many properties native NMDA receptors are with homomeric NR1 expressed Xenopus oocytes, we have found differentially regulated by NR2 subunits heteromeric NR1/NR2 receptors. Glycine-independent stimulation occurred at NR1A receptors, which lack amino-terminal insert NR1, NR1A/NR2B but not NR1A/NR2A or NR1A/NR2C was NR1B containing NR1B. Thus, glycine-independent polyamines requires variant, such as NR1A, lacks insert, manifestation stimulatory effect controlled type subunit present a complex. Glycine-dependent may therefore involve second binding site distinct from produces stimulation. inhibitory spermine, more pronounced hyperpolarized membrane potentials, similar magnitudes absent control both Stimulation inhibition extracellular Mg2+. Stimulation, physiological Ca2+ Mg2+, be predominant intact nervous system.