Activation of DOR attenuates anoxic K+ derangement via inhibition of Na+ entry in mouse cortex.
We have recently found that in the mouse cortex, activation of delta-opioid receptor (DOR) attenuates the disruption of K(+) homeostasis induced by hypoxia or oxygen-glucose deprivation. This novel observation suggests that DOR may protect neurons from hypoxic/ischemic insults via the regulation of K(+) homeostasis because the disruption of K(+) homeostasis plays a critical role in neuronal injury under hypoxic/ischemic stress. The present study was performed to explore the ionic mechanism underlying the DOR-induced neuroprotection. Because anoxia causes Na(+) influx and thus stimulates K(+) leakage, we investigated whether DOR protects the cortex from anoxic K(+) derangement by targeting the Na(+)-based K(+) leakage. By using K(+)-sensitive microelectrodes in mouse cortical slices, we showed that 1) lowering Na(+) concentration and substituting with impermeable N-methyl-D-glucamine caused a concentration-dependent attenuation of anoxic K(+) derangement; 2) lowering Na(+) concentration by substituting with permeable Li(+) tended to potentiate the anoxic K(+) derangement; and 3) the DOR-induced protection against the anoxic K(+) responses was largely abolished by low-Na(+) perfusion irrespective of the substituted cation. We conclude that external Na(+) concentration greatly influences anoxic K(+) derangement and that DOR activation likely attenuates anoxic K(+) derangement induced by the Na(+)-activated mechanisms in the cortex.
Chao
Dongman
D
Department of Pediatrics, Section of Respiratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Bazzy-Asaad
Alia
A
Balboni
Gianfranco
G
Salvadori
Severo
S
Xia
Ying
Y
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology; D005971:Glutamates / Q000494:pharmacology; D006706:Homeostasis / Q000502:physiology; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000503:physiopathology*; D008094:Lithium / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011188:Potassium / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000502:physiology*; D012964:Sodium / Q000493:pharmacokinetics*
D005971:Glutamates; D017465:Receptors, Opioid, delta; C014574:gamma-glutamylmethylamide; D008094:Lithium; D012964:Sodium; D011188:Potassium