Increased contribution of N-methyl-D-aspartate receptors to synaptic transmission inCA1 area of the rat hippocampus after short-term episodes of hypoxia/aglycemia

Effect of hypoxia/aglycemia episodes on excitatory postsynaptic currents (EPSC) evoked in pyramidal neurons of the rat hippocampalCA1 area by electrical stimulation of Schaffer collaterals was studied using voltage-clamp and intracellular perfusion techniques. By 60–80 min after a 10-min-long hypoxia/aglycemia episode, the EPSC amplitude increased and the EPSC decay was considerably slowed down, if compared with control. In contrast to control conditions, under which EPSC decay kinetics did not depend on the stimulus strength, hypoxia/aglycemia was followed by slowing down of the EPSC decay when stimulus intensity increased. The stimulus-dependent posthypoxic “slow” EPSC component was depressed both by D-(−)-2-amino-5-phosphonovaleric acid, an NMDA receptor blocker, and by 6-cyano-7-nitroquinoline-2,3-dion, a non-NMDA receptor blocker, which suggested possible polysynaptic origin of the above EPSC component. We suggest that short-term hypoxia/aglycemia transforms into an active state the NMDA receptors in the synapses of excitatory reccurrent collaterals of theCA1 hippocampal area, which had not functioned before. An increase in the intracellular calcium concentration from 1.5 to 5.0 mM resulted in the effect similar to that produced by hypoxia/aglycemia, which suggests that calcium channels play an important role in the mechanisms responsible for hypoxia-related activation of “silent” NMDA receptors.