Biophysical and molecular properties of amiloride-inhibitable Na+ channels in alveolar epithelial cells

Sadis Matalon, Dale J. Benos, Robert M. Jackson

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Abstract

The recent immunopurification and cloning of various lung Na+ channel proteins has provided the necessary tools to study Na+ transport at a fundamental level across a number of epithelial tissues. Various macroscopic measurements of Na+ transport have shown that Na+ ions enter the cytoplasm of alveolar cells mainly through amiloride-inhibitable Na+ channels. Molecular biology studies have shown the existence of three Na+ channel subunit mRNAs (α-, β-, and γ-rENaC) in mature fetal (FDLE) and adult alveolar type II (ATII) cells. Patch-clamp studies have demonstrated the existence of various types of amiloride-inhibitable Na+ channels, located in the apical membranes of FDLE and ATII cells. β-Agonists and agents that enhance intracellular adenosine 3',5'-cyclic monophosphate levels increase the open probability of these channels, leading to increased Na+ transport across the alveolar epithelium in vivo. Immunopurification of a putative channel protein from adult ATII cells showed that it contains an amiloride- binding subunit with a molecular mass of 150 kDa. When this protein was reconstituted in planar lipid bilayers, it exhibited single channels with a conductance of 25 pS, which were moderately selective for Na+ over K+. The open probability of these channels was increased by the addition of protein kinase A (PKA) and ATP, and was decreased to the same extent by addition of [N-ethyl-N-isopropyl]-2'-4'-amiloride (EIPA) and amiloride (1 μM each) in the apical side of the bilayer, in agreement with the results of patch-clamp studies in ATII cells. Exposure of rats to sublethal hyperoxia increased α- rENaC mRNA and the functional expression of Na+ channels in alveolar epithelial cells and limited alveolar edema. These findings indicate that alveolar epithelial channels contain at least one family of amiloride- sensitive Na+ channel proteins, which displays a number of unique properties, including sensitivity to EIPA.

Original languageEnglish (US)
Pages (from-to)L1-L22
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume271
Issue number1 15-1
StatePublished - Sep 17 1996

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Keywords

  • α-rat epithelial sodium channel
  • alveolar type II cells
  • fetal alveolar cells
  • hormones agonists
  • immunocytochemistry
  • lipid bilayers
  • molecular biology
  • patch clamp
  • short-circuit current
  • sodium channel antibodies

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

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