Hypoxic activation of an amiloride-sensitive cation conductance in alveolar epithelial cells

Imposing hypoxia (P-o2 = 23 mmHg) upon A549 cells elicited increased G(amil ) although previous work had predicted a fall in this parameter. G(amil) ap peared to be dependent upon glucocorticoid-driven gene expression, a proces s inhibited by ERK, an enzyme activated by oxidative stress. However, hypox ia transiently activated this enzyme and the response was blocked by glucoc orticoids, showing that the rise in G(amil) occurs only if ERK activation i s suppressed. Fluorimetric assays showed that lowering P-o2 elicited H2O2 f ormation indicating that this maneuver actually imposes oxidative stress, t hus explaining how hypoxia can elicit responses normally associated with a rise in P-o2. (C) 2001 Academic Press.