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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/L537    most recent 00373.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Elias, N. Articles by O'Brodovich, H. Search for Related Content PubMed PubMed Citation Articles by Elias, N. Articles by O'Brodovich, H.

EDITORIAL FOCUS

The role of -, -, and -ENaC subunits in distal lung epithelial fluid absorption induced by pulmonary edema fluid

¹Program in Lung Biology, ²Division of Pathology, and ³Department of Pediatric Laboratory Medicine, Hospital for Sick Children Research Institute, Toronto; and Departments of ⁴Pediatrics, ⁵Physiology, and ⁶Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

Submitted 21 September 2006 ; accepted in final form 14 May 2007

Edema fluid (EF) increases epithelial Na⁺ transport by rat fetal distal lung epithelia (FDLE) and induces net lung fluid absorption in fetal mouse lung explants [Rafii B, Gillie DJ, Sulowski C, Hannam V, Cheung T, Otulakowski G, Barker PM, O'Brodovich H. J Physiol (Lond) 544: 537–548, 2002]. We now show that EF increases fluid absorption across monolayers of rat FDLE in a dose-dependent manner. To study the role of subunits of the epithelial Na⁺ channel (ENaC) in the phenomena, we cultured explants from the distal lungs of 16-day gestational age wild-type (WT) or -, -, or -ENaC knockout or heterozygote (HT) mice. WT explants cultured in media continuously expanded over time as a result of net fluid secretion. In contrast, when explants were exposed to EF for 24 h, net fluid absorption occurred. EF-exposed explants had normal histology, but marked changes were seen after Triton X-100 or staurosporine exposure. Transmission electron microscopy showed EF promoted lamellar body formation and abundant surfactant in the explants' lumens. EF-induced changes in explant size were similar in -ENaC knockout, WT, and HT littermate fetal lung explants (P > 0.05). In contrast, EF's effect was attenuated in - and -ENaC knockouts (P < 0.05) vs. WT and HT littermate fetal lung explants. EF exposure slightly decreased or had no effect on mRNA levels for -ENaC in various mouse genotypes but decreased expression of - and -ENaC subunit mRNAs (P < 0.01) across all genotype groups. We conclude that - and -, but not -, ENaC subunits are essential for EF to exert its maximal effect on net fluid absorption by distal lung epithelia.

epithelium; Na⁺ transport; lung development; amiloride-sensitive epithelial Na⁺ channel

This article has been cited by other articles:

				H. O'Brodovich, P. Yang, S. Gandhi, and G. Otulakowski Amiloride-insensitive Na+ and fluid absorption in the mammalian distal lung Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L401 - L408. [Abstract] [Full Text] [PDF]