Alterations of N-methyl-D-aspartate receptor properties after chemical ischemia

Sublethal ischemic challenges can protect neurons against a second, more se vere hypoxic insult. We report here that nonlethal chemical ischemia induce s a transient alteration of NMDA receptors in rat cortical neurons in cultu re. Cells were incubated with 3 mM KCN in a glucose-free solution for 90 mi n. Analysis of NMDA receptor unitary events in patches excised from KCN-tre ated neurons showed an increased incidence of a small conductance channel 2 4 h after chemical ischemia. Whole-cell recordings of NMDA-induced currents 1 day after cyanide exposure revealed a significant increase in voltage-de pendent extracellular Mg2+ block compared with untreated neurons. The block reverted to control levels within 48 h. Both of these changes in the NMDA receptor could decrease the overall current flowing through the channel. Me ssage levels for the NMDA receptor subunits NR1, NR2A, and NR2B were not di fferent between the chemically challenged neurons and control cells, wherea s NR2C message was barely detectable in either group. These results suggest that the alterations in NMDA receptor properties after KCN exposure may co ntribute to the molecular mechanisms that are activated in neurons to withs tand lethal ischemic events in the brain after preconditioning.