Inhibition of na, k-atpase activity after prolonged hypoxia in an
alveolar epithelial cell line.
Plan[grave]es, Carole, G[acute]erard Friedlander, Alain Loiseau,
Claude Amiel, and Christine Clerici.
Department of Physiology and INSERM U 426, Facult[acute]e de
M[acute]edecine Xavier Bichat, Universit[acute]e Denis Diderot, Paris
7, 75018 Paris, France
APStracts 3:0033L, 1996.
Exposure to alveolar hypoxia may induce acute pulmonary edema. Since
the vectorial sodium transport by alveolar epithelium represents an
important mechanism for alveolar edema clearance, we examined whether
hypoxia affects Na,K-ATPase activity in cultured SV 40 transformed
rat alveolar type II cells (SV 40 ATII cells). Hypoxic exposures (0%
or 5% O2 for at least 12 h) induced a time- and O2 concentration
-dependent decrease in ouabain-sensitive rubidium (OsRb) influx.
Neither the sensitivity of Rb influx to ouabain nor the maximum
velocity of the enzyme measured on crude cell homogenates were
affected by hypoxia. OsRb influx decrease was independent of hypoxia
-induced ATP depletion. Na,K-ATPase inhibition was most likely related
to impaired calcium homeostasis since 1) calcium influx was increased
in hypoxic cells, 2) hypoxia-induced OsRb influx decrease was
completely prevented by nifedipine (10-5 M), 3) OsRb influx decreased
in normoxic cells incubated with ionomycine (10-6 M, 15 min.).
Furthermore, hypoxia-induced Na,K-ATPase impairment might be due, at
least in part, to the endogenous release by hypoxic cells of a
lipidic factor in extracellular medium since incubation of normoxic
cells with hypoxic cells conditioned medium, or with the lipidic
subphase from hypoxic cells-conditioned medium, also induced a
partial decrease in OsRb influx. This decrease was associated with
increased calcium influx into normoxic cells and was suppressed
either by the removal of external calcium or by nifedipine,
suggesting that the lipidic factor exerted its inhibitory action on
Na,K-ATPase via an enhancement of calcium entry. These results
indicate that prolonged hypoxic exposure impairs Na,K-ATPase activity
in SV 40 transformed rat ATII cells and may therefore decrease the
vectorial sodium transport by alveolar epithelium.
Received 8 November 1995; accepted in final form 9 February 1996.
APS Manuscript Number L318-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96