Hypoxia-effects on Ca-i-signaling and ion transport activity of lung alveolar epithelial cells

In excitatory cells specific responses upon changes in PO2 are mediated by changes in intracellular Ca (Ca). We wanted to know whether ion transport o f lung alveolar epithelial cells is regulated by Cal and whether Ca-I and C a-I-signaling are affected by hypoxia in a way that might explain hypoxic t ransport inhibition (Mairbaurl et al. AJP 273: L797, 1997). The activity of transport (Na/K-pump, Na/K/2Cl-cotransport) was measured as unidirectional Rb-86-uptake after A549 cells were exposed to hypoxia (3% O-2). Ca-I of pr imary cultured rat alveolar type II cells was measured by fura-2 epifluores cence. Depletion of Ca, by extracellular chelators in presence of ionomycin or with thapsigargin as well as PKC inhibition decreases Rb-86-uptake of n ormoxic and hypoxic A549 cells, whereas an increased Ca, activates transpor t. Neither immediate nor prolonged exposure to hypoxia changes Ca, signific antly. The increase in Ca, upon stimulation with ATP, which is caused mainl y by release from intracellular stores, is smaller in hypoxia than in normo xia. These results indicate that ion transport of alveolar epithelial cells is modulated by Ca,. A change in Ca, does not mediate hypoxic transport in hibition. The decreased Cal transients in hypoxia might indicate a blunted response to extracellular stimuli. Copyright (C) 2001 S. Karger AG, Basel.