Skip Navigation



Cerebral Cortex Advance Access published online on January 17, 2008
Cerebral Cortex, doi:10.1093/cercor/bhm247
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Chao, D.
Right arrow Articles by Xia, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chao, D.
Right arrow Articles by Xia, Y.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Activation of DOR Attenuates Anoxic K+ Derangement via Inhibition of Na+ Entry in Mouse Cortex

Dongman Chao1, Alia Bazzy-Asaad1, Gianfranco Balboni2,3, Severo Salvadori3 and Ying Xia1

1 Department of Pediatrics, Section of Respiratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA, 2 Department of Toxicology, University of Cagliari, I-09124 Cagliari, Italy, 3 Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, I-44100 Ferrara, Italy

Address correspondence to Ying Xia, MD, PhD, Yale University School of Medicine, Department of Pediatrics, 333 Cedar Street, LMP 3107, New Haven, CT 06520, USA. Email: ying.xia{at}yale.edu.

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.

Key Words: anoxia • cortex • {delta}-opioid receptor • K+ homeostasis • Na+ influx • neuroprotection


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.