The NMDA subtype of glutamate receptor is sensitive to reducing and oxidizing agents in a subtype specific-manner. Cysteines 744 and 798 on NR1a are responsible for most of the redox sensitivity of NR1a/NR2B and NR1a/NR2C receptors. However, NR1a(c744a/c798a)/NR2A receptors remain sensitive to redox modulation. This has been attributed to cysteines in the amino terminal domain (ATD) of NR1 and NR2A (Choi et al., J. Neurosci. 21:392;2001). We have previously shown that 30uM spermine blocks the effects of DTT in NR1a(c744a,c798a)/NR2A receptors (Herin et al., SFN Abstracts 703.12; 2001), in a tricine-insensitive manner. This suggests a zinc-independent effect of spermine on redox modulation at the N-terminal redox-sensitive cysteines. Evidence exists that spermine alone modulates NR1a/NR2B (but not NR1a/NR2A) receptors via the N-terminal regulatory domain of NR1a. We hypothesized that spermine block of DTT potentiation in NR1a(c744a/c798a)/NR2A could be modified by alterations of the ATD of NR1a. Mutation of...