Research Article

Cellular and Molecular Life Sciences

, Volume 66, Issue 21, pp 3505-3516

δ-Opioid receptors protect from anoxic disruption of Na+ homeostasis via Na+ channel regulation

  • Xuezhi KangAffiliated withShanghai Research Center for Acupuncture and Meridians
  • , Dongman ChaoAffiliated withYale University School of Medicine
  • , Quanbao GuAffiliated withShanghai Research Center for Acupuncture and Meridians
  • , Guanghong DingAffiliated withShanghai Research Center for Acupuncture and Meridians
  • , Yingwei WangAffiliated withShanghai Jiaotong University College of Medicine
  • , Gianfranco BalboniAffiliated withUniversity of Cagliari
  • , Lawrence H. LazarusAffiliated withNational Institute of Environmental Health Sciences
  • , Ying XiaAffiliated withYale University School of Medicine Email author 

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Abstract

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 δ-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.

Keywords

δ-Opioid receptor Na+ channels Na+ influx Hypoxia Cortex