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1 Departments of Anesthesiology
and Biomedical Engineering,
Alveolar epithelial cells effect edema clearance by transporting Na+ and liquid out of the air spaces. Active Na+ transport by the basolaterally located Na+-K+-ATPase is an important contributor to lung edema clearance. Because alveoli undergo cyclic stretch in vivo, we investigated the role of cyclic stretch in the regulation of Na+-K+-ATPase activity in alveolar epithelial cells. Using the Flexercell Strain Unit, we exposed a cell line of murine lung epithelial cells (MLE-12) to cyclic stretch (30 cycles/min). After 15 min of stretch (10% mean strain), there was no change in Na+-K+-ATPase activity, as assessed by 86Rb+ uptake. By 30 min and after 60 min, Na+-K+-ATPase activity was significantly increased. When cells were treated with amiloride to block amiloride-sensitive Na+ entry into cells or when cells were treated with gadolinium to block stretch-activated, nonselective cation channels, there was no stimulation of Na+-K+-ATPase activity by cyclic stretch. Conversely, cells exposed to Nystatin, which increases Na+ entry into cells, demonstrated increased Na+-K+-ATPase activity. The changes in Na+-K+-ATPase activity were paralleled by increased Na+-K+-ATPase protein in the basolateral membrane of MLE-12 cells. Thus, in MLE-12 cells, short-term cyclic stretch stimulates Na+-K+-ATPase activity, most likely by increasing intracellular Na+ and by recruitment of Na+-K+-ATPase subunits from intracellular pools to the basolateral membrane.
sodium transport; amiloride; gadolinium; Nystatin; pulmonary edema; mechanical ventilation; sodium-potassium-adenosine 5'-triphosphatase
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