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Am J Physiol. 1996 Jul;271(1 Pt 1):L70-8.

Inhibition of Na-K-ATPase activity after prolonged hypoxia in an alveolar epithelial cell line.

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Department of Physiology, Faculté de Médecine Xavier Bichat, Université Denis Diderot, Paris, France.


Exposure to alveolar hypoxia may induce acute pulmonary edema. Because 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 SV40-transformed rat alveolar type II cells (SV40 ATII cells). Hypoxic exposures (O 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 was affected by hypoxia. The osRb influx decrease was independent of hypoxia-induced ATP depletion. Na-K-ATPase inhibition was most likely related to impaired calcium homeostasis, because 1) calcium influx was increased in hypoxic cells, 2) hypoxia-induced osRb influx decrease was completely prevented by nifedipine (10-5 M), and 3) osRb influx decreased in normoxic cells incubated with ionomycin (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, because incubation of normoxic cells with hypoxic cells conditioned medium (CM), or with the lipidic subphase from hypoxic cells CM, 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 SV40 ATII cells and may therefore decrease the vectorial sodium transport by alveolar epithelium.

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