Differential expression of Na-K-ATPase isoforms in rat alveolar epithelial cells

Karen M. Ridge*, David H. Rutschman, Phillip Factor, Adrian I. Katz, Alejandro M. Bertorello, J. Iasha Sznajder

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Lung Na-K-ATPase has been shown to contribute to vectorial Na+ transport and edema clearance. The α1- and β1-Na-K-ATPase subunits have been localized to alveolar type II (ATII) cells, and the α2-Na-K-ATPase has been reported in rat lung homogenates. Expression of Na-K-ATPase α1-, α2- , and β1-subunits was investigated in rat ATII cells cultured for 7 days, a period during which they lose their phenotypic markers and differentiate to an alveolar type I (ATI)-like cell phenotype. Differentiation of ATII cells to an ATI-like phenotype resulted in a decrease of α1- and an increase of α2-mRNA and protein abundance without changes in the β1-subunit. Thus ATI-like cells exhibited a mixture of α1- and α2-isoforms. Nuclear run- on analysis suggests that these changes were transcriptionally regulated. The existence of the distinct functional classes of Na-K-ATPase in ATII and ATI- like cells was confirmed by ouabain inhibition of Na-K-ATPase activity. Ouabain inhibition of ATII cells was consistent with expression of the α1- isozyme [50% inhibitory concentration (IC50) = 4 x 10-5 M], whereas, in ATI-like cells, it was consistent with the presence of both α1- and α2- isozymes (IC50 = 9.0 x 10-5 and 1.5 x 10-7 M, respectively); [3H]ouabain binding studies corroborated these findings. Our results indicate that, during ATII cell cytodifferentiation with time in culture, there is a shift in isoform composition that may reflect physiological functions of alveolar epithelial cells.

Original languageEnglish (US)
Pages (from-to)L246-L255
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume273
Issue number1 17-1
DOIs
StatePublished - Jul 1997

Keywords

  • Active transport
  • Cytodifferentiation
  • Kinetics
  • Ouabain
  • Sodium-potassium-adenosinetriphosphatase subunits

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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