Cellular and Molecular Life Sciences

, Volume 66, Issue 6, pp 1105–1115

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

  • D. Chao
  • G. Balboni
  • L. H. Lazarus
  • S. Salvadori
  • Y. Xia
Research Article

DOI: 10.1007/s00018-009-8759-5

Cite this article as:
Chao, D., Balboni, G., Lazarus, L.H. et al. Cell. Mol. Life Sci. (2009) 66: 1105. doi:10.1007/s00018-009-8759-5

Abstract.

Activation of δ-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+/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 anoxic K+ derangement in certain degrees, are less likely the targets of DOR signal.

Keywords.

Anoxiacortexδ-opioid receptorK+ homeostasisNa+ channelsionotropic glutamate receptor channels

Copyright information

© Birkhäuser Verlag, Basel 2009

Authors and Affiliations

  • D. Chao
    • 1
  • G. Balboni
    • 2
    • 3
  • L. H. Lazarus
    • 3
  • S. Salvadori
    • 4
  • Y. Xia
    • 1
  1. 1.Department of PediatricsYale University School of MedicineNew HavenUSA
  2. 2.Department of ToxicologyUniversity of CagliariCagliariItaly
  3. 3.Medicinal Chemistry Group, Laboratory of PharmacologyNational Institute of Environmental Health SciencesResearch Triangle ParkUSA
  4. 4.Department of Pharmaceutical Sciences and Biotechnology CenterUniversity of FerraraFerraraItaly