Hypoxia-effects on Ca(i)-signaling and ion transport activity of lung alveolar epithelial cells.
In excitatory cells specific responses upon changes in PO(2) are mediated by changes in intracellular Ca (Ca(i)). We wanted to know whether ion transport of lung alveolar epithelial cells is regulated by Ca(i) and whether Ca(i) and Ca(i) -signaling are affected by hypoxia in a way that might explain hypoxic transport inhibition (Mairbäurl et al. AJP 273: L797, 1997). The activity of transport (Na/K-pump, Na/K/2Cl-cotransport) was measured as unidirectional (86)Rb-uptake after A549 cells were exposed to hypoxia (3% O(2)). Ca(i) of primary cultured rat alveolar type II cells was measured by fura-2 epifluorescence. Depletion of Ca(i) by extracellular chelators in presence of ionomycin or with thapsigargin as well as PKC inhibition decreases (86)Rb-uptake of normoxic and hypoxic A549 cells, whereas an increased Ca(i) activates transport. Neither immediate nor prolonged exposure to hypoxia changes Ca(i) significantly. The increase in Ca(i) upon stimulation with ATP, which is caused mainly by release from intracellular stores, is smaller in hypoxia than in normoxia. These results indicate that ion transport of alveolar epithelial cells is modulated by Ca(i). A change in Ca(i) does not mediate hypoxic transport inhibition. The decreased Ca(i) transients in hypoxia might indicate a blunted response to extracellular stimuli.
Papen
M
M
Medical Clinic, Section VII, Sports Medicine, University of Heidelberg, Germany.
Wodopia
R
R
Bärtsch
P
P
Mairbäurl
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D028021:Sodium-Potassium-Chloride Symporters; D015759:Ionomycin; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D002118:Calcium