AJP - Cell Physiology, Vol 262, Issue 2 C358-C364, Copyright © 1992 by American Physiological Society

ARTICLES

Hyperoxia induces alkalinization and dome formation in MDCK epithelial cells

D. Dreher and T. Rochat
Respiratory Division, University Hospital, Geneva, Switzerland.

We observed that confluent Madin-Darby canine kidney (MDCK) epithelial cells exposed to 95% O2 showed intensive dome formation, a manifestation of cell differentiation and transepithelial fluid transport, whereas cells exposed to 40% O2 or to normoxia did not. Hyperoxia-induced dome formation (HIDF) was preceded and accompanied by a significant rise in intracellular pH (pHi) on days 2 (7.53 vs. 7.42) and 3 (7.62 vs. 7.45), as compared with controls. Inhibition of the Na(+)-H+ exchanger by 0.1 or 1.0 mM amiloride caused 29 or 69% reduction of HIDF and completely abolished hyperoxia-induced alkalinization of the cells. HIDF was altered by modification of extracellular pH (pHo); there was a decrease by 84% with pHo 6.8, while pHo 7.8 led to earlier and more intensive dome formation (day 2, +472%; day 3, +27%). We also found that adenosine 3',5'-cyclic monophosphate (cAMP) was increased in hyperoxic cells, a change that was independent from the rise of pHi. We conclude that high-level hyperoxia induces dome formation in MDCK epithelial monolayers by a process involving activation of the Na(+)-H+ exchanger, together with increased intracellular cAMP.

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