Mechanical stretching of alveolar epithelial cells increases Na1-K1-ATPase activity

Waters, Christopher M., Karen M. Ridge, G. Sunio, K. Venetsanou, and Jacob Iasha Sznajder. Mechanical stretching of alveolar epithelial cells increases Na1-K1ATPase activity. J. Appl. Physiol. 87(2): 715–721, 1999.— Alveolar epithelial cells effect edema clearance by transporting Na1 and liquid out of the air spaces. Active Na1 transport by the basolaterally located Na1-K1-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 Na1-K1-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 Na1-K1-ATPase activity, as assessed by 86Rb1 uptake. By 30 min and after 60 min, Na1-K1-ATPase activity was significantly increased. When cells were treated with amiloride to block amiloride-sensitive Na1 entry into cells or when cells were treated with gadolinium to block stretch-activated, nonselective cation channels, there was no stimulation of Na1-K1-ATPase activity by cyclic stretch. Conversely, cells exposed to Nystatin, which increases Na1 entry into cells, demonstrated increased Na1-K1ATPase activity. The changes in Na1-K1-ATPase activity were paralleled by increased Na1-K1-ATPase protein in the basolateral membrane of MLE-12 cells. Thus, in MLE-12 cells, short-term cyclic stretch stimulates Na1-K1-ATPase activity, most likely by increasing intracellular Na1 and by recruitment of Na1-K1-ATPase subunits from intracellular pools to the basolateral membrane.