Na+ mechanism of delta-opioid receptor induced protection from K+ leakage in the cortex

Activation of d-opioid receptors (DOR) attenuates anoxic K+ leakage and protects cortical neurons from anoxic insults by inhibiting Na+ influx. It is unknown, however, which pathway(s) thatmediates the Na+ influx is the target of DOR signal. In the present work, we found that, in the cortex, (1) DOR protection was largely dependent on the inhibition of anoxic Na+ influxes mediated by voltage-gated Na+ channels; (2) DOR activation inhibited Na+ influx mediated by ionotropic glutamate N-methyl-D-aspartate (NMDA) receptors, but not that by non-NMDA receptors, although both played a role in anoxic K+ derangement; and (3)DORactivation had little effect on Na+/Ca2+ exchanger-based response to anoxia.We conclude that DOR activation attenuates anoxic K+ derangement by restricting Na+ influx mediated by Na+ channels and NMDA receptors, and that non- NMDA receptors and Na+/Ca2+ exchangers, although involved in anoxicK+ derangement in certain degrees, are less likely the targets of DOR signal.