High CO2 levels impair alveolar epithelial function independently of pH

• Published in: PloS one Vol. 2; no. 11; p. e1238
• Main Authors: Briva, Arturo, Vadász, István, Lecuona, Emilia, Welch, Lynn C, Chen, Jiwang, Dada, Laura A, Trejo, Humberto E, Dumasius, Vidas, Azzam, Zaher S, Myrianthefs, Pavlos M, Batlle, Daniel, Gruenbaum, Yosef, Sznajder, Jacob I
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-11-2007; Public Library of Science (PLoS)
• Subjects: Accumulation; Alveoli; Animals; Body Fluids; Carbon dioxide; Carbon Monoxide - metabolism; Critical care; Critical Care and Emergency Medicine; Dopamine; Edema; Energy consumption; Energy utilization; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - enzymology; Gas exchange; Homeostasis; Hydrogen ions; Hydrogen-Ion Concentration; Hypercapnia; Intracellular; Kinases; Lung diseases; Lungs; Male; Mammalian cells; Mammals; Mechanical ventilation; Medicine; Metabolism; Na+/K+-exchanging ATPase; Patients; pH effects; Phosphatase; Phosphorylation; Physiology; Plasma; Protein kinase C; Proteins; Pulmonary Alveoli - cytology; Pulmonary Alveoli - enzymology; Pulmonary Alveoli - physiology; Rats; Rats, Sprague-Dawley; Reabsorption; Respiratory Medicine; Rodents; Signaling; Smooth muscle; Sodium-Potassium-Exchanging ATPase - chemistry; Sodium-Potassium-Exchanging ATPase - metabolism; Ventilation; Ventilators; United States > US; Illinois; Chicago Illinois
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0001238

In patients with acute respiratory failure, gas exchange is impaired due to the accumulation of fluid in the lung airspaces. This life-threatening syndrome is treated with mechanical ventilation, which is adjusted to maintain gas exchange, but can be associated with the accumulation of carbon dioxide in the lung. Carbon dioxide (CO2) is a by-product of cellular energy utilization and its elimination is affected via alveolar epithelial cells. Signaling pathways sensitive to changes in CO2 levels were described in plants and neuronal mammalian cells. However, it has not been fully elucidated whether non-neuronal cells sense and respond to CO2. The Na,K-ATPase consumes approximately 40% of the cellular metabolism to maintain cell homeostasis. Our study examines the effects of increased pCO2 on the epithelial Na,K-ATPase a major contributor to alveolar fluid reabsorption which is a marker of alveolar epithelial function.
We found that short-term increases in pCO2 impaired alveolar fluid reabsorption in rats. Also, we provide evidence that non-excitable, alveolar epithelial cells sense and respond to high levels of CO2, independently of extracellular and intracellular pH, by inhibiting Na,K-ATPase function, via activation of PKCzeta which phosphorylates the Na,K-ATPase, causing it to endocytose from the plasma membrane into intracellular pools.
Our data suggest that alveolar epithelial cells, through which CO2 is eliminated in mammals, are highly sensitive to hypercapnia. Elevated CO2 levels impair alveolar epithelial function, independently of pH, which is relevant in patients with lung diseases and altered alveolar gas exchange.