Na+ mechanism of delta-opioid receptor induced protection from anoxic K+ leakage in the cortex.
Activation of delta-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) that mediates 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) DOR activation had little effect on Na(+)/Ca(2+) 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(+)/Ca(2+) exchangers, although involved in anoxic K(+) derangement in certain degrees, are less likely the targets of DOR signal.
Chao
D
D
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.
Balboni
G
G
Lazarus
L H
LH
Salvadori
S
S
Xia
Y
Y
D000818:Animals; D002414:Cations, Monovalent; D002540:Cerebral Cortex / Q000502:physiology*; D002534:Hypoxia, Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology
D002414:Cations, Monovalent; D016194:Receptors, N-Methyl-D-Aspartate; D017465:Receptors, Opioid, delta; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D011188:Potassium