title: Mechanical stretching of alveolar epithelial cells increases Na(+)-K(+)-ATPase activity.
abstract: 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 (86)Rb(+) 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.
authors.affiliation: Departments of Anesthesiology and Biomedical Engineering, Northwestern University, Chicago 60611, Illinois. cwaters@physio1.utmem.edu
authors.forename: C M
authors.initials: CM
authors.lastname: Waters
authors.forename: K M
authors.initials: KM
authors.lastname: Ridge
authors.forename: G
authors.initials: G
authors.lastname: Sunio
authors.forename: K
authors.initials: K
authors.lastname: Venetsanou
authors.forename: J I
authors.initials: JI
authors.lastname: Sznajder
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology; D051379:Mice; D009761:Nystatin / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011661:Pulmonary Stretch Receptors / Q000502:physiology*; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D009761:Nystatin; D000584:Amiloride; D000255:Adenosine Triphosphate; D012964:Sodium; D005682:Gadolinium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium