Calmodulin (CALM1), activated by binding to calcium ions (Ca2+), after influx of calcium through the pore of activated GluN1:GluN2 (GRIN1:GRIN2) NMDA receptors, binds to the GluN1 (GRIN1, NR1) subunit of the NMDA receptors (Ehlers et al. 1995). Binding of calcium-calmodulin complex (CALM1:4xCa2+) competes with binding of alpha-actinin-2 (ACTN2) to GluN1, leading to dissociation of NMDA receptors from ACTN2 (Wyszynski et al. 1997). Calmodulin binding inhibits the activity of NMDA receptors by reducing the duration of the channel pore open state (Ehlers et al. 1996) and possibly by interfering with ACTN2-mediated anchoring of NMDA receptors to the postsynaptic density (Wyszynski et al. 1997).