Low sodium injury in the hippocampal slice is mediated through NMDA receptors

Perfusion of hippocampal slices with normoxic medium containing no added sodium resulted in a rapid loss of the CA1 population spike, with only 35 +/- 10% (S.E.M.) (P < 0.001) recovery after a 15 min exposure. This injury was prevented by the non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 (93 +/- 4% recovery, P < 0.001), suggesting that low sodium injury may be mediated by opening of the NMDA receptor-associated ionic channels, possibly secondary to the well known sodium dependency of transmitter uptake systems. By contrast, slice perfusion with a medium moderately low in sodium (26 mM) produced only slight injury to the CA1 population spike under normoxic conditions (76 +/- 8% recovery) and provided no protection against hypoxic injury. Low chloride medium also provided no protection against hypoxic injury.