Hypoxia Augments Na+-K+-Cl-Cotransport Activity in Cultured Brain Capillary Endothelial Cells of the Rat

  • Nobutoshi Kawai
  • Richard M. McCarron
  • Maria Spatz
Part of the Advances in Behavioral Biology book series (ABBI, volume 46)

Summary

The effect of hypoxia on K+ uptake activity in cultured rat brain capillary endothelial cells (RBEC) was investigated by using 86Rb+ as a tracer for K+ Exposure of RBEC to hypoxia (95% N2/5% CO2, 24 hr) reduced Na+,K+-ATPase activity by 39%, whereas it significantly increased Na+-K+-Cl- cotransport activity by 48%. Exposure of RBEC to oligomycin, a metabolic inhibitor, led to a complete inhibition of Na+,K+-ATPase and a coordinated increase of Na+-K+-Cl- cotransport activity up to 2-fold. Oligomycin also increased the rate of K+ efflux. The reduction of oligomycin-augmented Na+-K+-Cl- cotransport activity by protein-tyrosine kinase inhibitors (genistein, 50 µM; herbimycin A, 10 µM) and the ineffectiveness of inhibitors of either protein kinase C (bisindolylmaleimide, 500 nM) or protein kinase A (H8, 20 µM) indicate the involvement of protein-tyrosine phosphorylation in this event. The data suggest that under hypoxic conditions when Na+,K+-ATPase activity is reduced, RBEC have the ability to increase K+ uptake through activation of Na+-K+-Cl- cotransport.

Keywords

ATPase Activity Brain Capillary Endothelial Cell Cotransport Activity Turnover Cycle Ischemic Brain Edema7 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Résumé

Nous avons étudié l’effet de l’hypoxie sur la capture du potassium par des cultures de cellules endothéliales de capillaires cérébraux de rat en utilisant le radioélement 86 Rb+ comme traceur du potassium. L’incubation des cultures en milieu hypoxique (95% N2/ 5% CO2) pendant 24 heures réduit l’activité du transporteur Na K ATP- dépendant de 39% tandis qu’elle augmente le cotransport Na,K,C1 de 48%. Le traitement des cellules par l'oligomycine, un inhibiteur métabolique, conduit à une complète inhibition du transporteur Na,K et une augmentation simultanée de 100% du cotransport Na, Cl, K. L’oligomycine augmente aussi l’efflux de potassium. L’induction de l’activité du cotransport Na, K, Cl peut être inhibée par des inhibiteurs de protéine tyrosine kinase (génistéine, 50µM; herbimycine A, 10 µM) mais pas par des inhibiteurs de protéine kinase C (bisindolylmaléimide, 500 nM) ou de protéine kinase A (H8, 20 µM). Ceci semble montrer que la phosphorylation de protéines par des protéine kinases intervient dans l’induction de ce cotransporteur. ces résultats suggèrent que, soumises à des conditions d’hypoxie, les cellules endothéliales cérébrales ont la possibité de compenser la diminution de l’activité du transporteur Na K par l'induction de l’activité du cotransporteur Na K Cl.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Nobutoshi Kawai
    • 1
  • Richard M. McCarron
    • 1
  • Maria Spatz
    • 1
  1. 1.Stroke BranchNINDS, NIHBethesdaUSA

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