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

• Published in: Cellular and molecular life sciences : CMLS Vol. 66; no. 6; pp. 1105 - 1115
• Main Authors: Chao, D, Balboni, G, Lazarus, L. H, Salvadori, S, Xia, Y
• Format: Journal Article
• Language: English
• Published: Basel Basel : Birkhäuser-Verlag 01.03.2009; Birkhäuser-Verlag
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cations, Monovalent; Cell Biology; Cerebral Cortex - physiology; cortex; hypoxia; Hypoxia, Brain - metabolism; In Vitro Techniques; Ion Channel Gating; ionotropic glutamate receptor channels; K⁺ homeostasis; Life Sciences; Male; Mice; Mice, Inbred C57BL; Na⁺ channels; Neurons - physiology; Potassium - metabolism; Receptors, N-Methyl-D-Aspartate - physiology; Receptors, Opioid, delta - drug effects; Receptors, Opioid, delta - physiology; Research Article; Sodium - metabolism; Sodium Channels - physiology; Sodium-Calcium Exchanger - physiology; δ-opioid receptor; cortex; homeostasis; Anoxia; Na; channels; δ-opioid receptor; K; ionotropic glutamate receptor channels
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-009-8759-5

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.