Nitric oxide mediates the sustained opening of NMDA receptor-gated ionic channels which follows transient excitotoxic exposure in hippocampal slices.

In the rat hippocampal slice, a brief exposure to glutamate and glycine increased MK-801 binding to 246% of controls. Increased binding persisted 90 min after removal of those amino acids from the incubation medium. Posttreatment with the competitive substrate inhibitor of nitric oxide synthase, N omega-nitro-L-arginine or with hemoglobin, which binds NO extracellularly, inhibited this postexcitotoxic increase in MK-801 binding. L-Arginine reversed this inhibitory effect but D-arginine did not. The combination of tetrodotoxin and low Ca2+, which blocks transmitter release prevented the poststimulation increase in MK-801 binding, suggesting a presynaptic component. These findings suggest that the sustained opening of NMDA receptor-gated ionic channels seen after transient glutamate/glycine stimulation is mediated by NO.