Increased expression and activity of sodium channels in alveolar type II cells of hyperoxic rats

Gang Yue, William J. Russell, Dale J. Benos, Robert M. Jackson, Mitchell A. Olman, Sadis Matalon

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

We investigated the cellular and molecular events associated with the increase in sodium transport across the alveolar epithelium of rats exposed to hyperoxia (85% O2 for 7 days followed by 100% O2 for 4 days). Alveolar type II (ATII) cell RNA was isolated and probed with a cDNA for one of the rat colonic epithelial sodium channel subunits (αrENaC). The αrENaC mRNA (3.7-kb transcript) increased 3-fold in ATII cell RNA isolated from rats exposed to 85% O2 for 7 days and 6-fold after 4 days of subsequent exposure to 100% O2. In situ hybridization revealed increased expression of αrENaC mRNA transcripts in both airway and alveolar epithelial cells of hyperoxic rats. When immunostained with a polyclonal antibody to kidney sodium channel protein, ATII cells from hyperoxic rats exhibited a significant increase in the amount of immunogenic protein present in both the plasma membrane and the cytoplasm. When patched in the whole-cell mode, ATII cells from hyperoxic rats exhibited amiloride and 5-(N-ethyl-N-isopropyl)-2',4'-amiloride (EIPA)sensitive currents that were 100% higher compared with those obtained from air-breathing rats. Single-channel sodium currents (mean conductance of 25 pS) were seen in ATII cells patched in both the inside-out and cell- attached modes. The number and open probability of these channels increased significantly during exposure to hyperoxia. Exposure to sublethal hyperoxia up-regulated both αrENaC mRNA and the functional expression of sodium channels in ATII cells.

Original languageEnglish (US)
Pages (from-to)8418-8422
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number18
DOIs
StatePublished - Aug 29 1995
Externally publishedYes

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Keywords

  • α subunit of rat epithelial Na channel
  • amiloride
  • ethylisopropylamiloride
  • immunofluorescence
  • in situ hybridization

ASJC Scopus subject areas

  • Genetics
  • General

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