delta-Opioid receptors protect from anoxic disruption of Na+ homeostasis via Na+ channel regulation.
Hypoxic/ischemic disruption of ionic homeostasis is a critical trigger of neuronal injury/death in the brain. There is, however, no promising strategy against such pathophysiologic change to protect the brain from hypoxic/ischemic injury. Here, we present a novel finding that activation of delta-opioid receptors (DOR) reduced anoxic Na+ influx in the mouse cortex, which was completely blocked by DOR antagonism with naltrindole. Furthermore, we co-expressed DOR and Na+ channels in Xenopus oocytes and showed that DOR expression and activation indeed play an inhibitory role in Na+ channel regulation by decreasing the amplitude of sodium currents and increasing activation threshold of Na+ channels. Our results suggest that DOR protects from anoxic disruption of Na+ homeostasis via Na+ channel regulation. These data may potentially have significant impacts on understanding the intrinsic mechanism of neuronal responses to stress and provide clues for better solutions of hypoxic/ischemic encephalopathy, and for the exploration of acupuncture mechanism since acupuncture activates opioid system.
Kang
Xuezhi
X
Shanghai Research Center for Acupuncture and Meridians, Shanghai, China.
Chao
Dongman
D
Gu
Quanbao
Q
Ding
Guanghong
G
Wang
Yingwei
Y
Balboni
Gianfranco
G
Lazarus
Lawrence H
LH
Xia
Ying
Y
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis
D017465:Receptors, Opioid, delta; D015222:Sodium Channels; D012964:Sodium; D010100:Oxygen