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Am J Physiol Lung Cell Mol Physiol 283: L737-L746, 2002. First published May 17, 2002; doi:10.1152/ajplung.00030.2001
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Vol. 283, Issue 4, L737-L746, October 2002

Na+-K+-ATPase activity in alveolar epithelial cells increases with cyclic stretch

Jacob L. Fisher and Susan S. Margulies

Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Na+-K+-ATPase pumps (Na+ pumps) in the alveolar epithelium create a transepithelial Na+ gradient crucial to keeping fluid from the pulmonary air space. We hypothesized that alveolar epithelial stretch stimulates Na+ pump trafficking to the basolateral membrane (BLM) and, thereby, increases overall Na+ pump activity. Alveolar type II cells were isolated from Sprague-Dawley rats and seeded onto elastic membranes coated with fibronectin or 5-day-conditioned extracellular matrix. After 2 days in culture, cells were uniformly stretched for 1 h in a custom-made device. Na+ pump activity was subsequently assessed by ouabain-inhibitable uptake of 86Rb+, a K+ tracer, and BLM Na+ pump abundance was measured. In support of our hypothesis, cells increased Na+ pump activity in a "dose-dependent" manner when stretched to 12, 25, or 37% change in surface area (Delta SA), and cells stretched to 25% Delta SA more than doubled Na+ pump abundance in the BLM. Cells on 5-day matrix tolerated higher strain than cells on fibronectin before the onset of Na+ pump upregulation. Treatment with Gd3+, a stretch-activated channel blocker, amiloride, a Na+ channel blocker, or both reduced but did not abolish stretch-induced effects. Sustained tonic stretch, unlike cyclic stretch, elicited no significant Na+ pump response.

ventilator-induced lung injury; alveolar edema; Na+-K+- ATPase; mechanical deformation; rubidium-86


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