Increased po2 alters the bioelectric properties of fetal distal
lung epithelium.
Pitk[umlaut]anen, Olli, A. Keith Tanswell, Gregory Downey, and Hugh
O'brodovich.
MRC Group in Lung Development (Hospital for Sick Children's
Research Institute's Respiratory and Neonatal Research Divisions),
Departments of Paediatrics and Internal Medicine of the University of
Toronto, Toronto, Ontario, Canada M5G-1X8
APStracts 3:0047L, 1996.
At birth the lung must efficiently clear the liquid from its airspaces
and permanently convert from a fluid secreting to a fluid absorbing
organ. When primary cultures of rat fetal distal lung epithelium
(FLDE) grown on permeable supports were switched from a fetal (3%) to
a postnatal (21%) oxygen environment there was an increase in
epithelial permeability as reflected by a dose dependent decline in
transepithelial resistance (R) 4 h later ( 3% = 239 + 19 [omega]*
cm2, 21% = 170 + 28 [omega]* cm2, 50% = 98 + 20 [omega]* cm2, p
< 0.05). The effect was transient since monolayers initially
maintained at 3% and switched to these higher oxygen concentrations
subsequently had R values comparable to the 3% group at 48 h (3% =
153 + 17 [omega]* cm2; 21% = 181 + 19 [omega]* cm2; 50% = 192 + 21
[omega]* cm2; p = n.s.). Changes in R were associated with expected
changes in the histologic appearance of the inter-epithelial tight
junctions but intracellular actin content and distribution remained
constant. Amiloride sensitive equivalent short circuit current
increased within 18 h, with further increases after 48 h of exposure
to postnatal oxygen concentrations. Ion substitution experiments
suggested diminished FDLE Cl transport and increased Na transport.
The amount of FDLE [alpha], [beta], and [delta]rENaC mRNA increased
within 48 h of increasing the ambient oxygen concentration. These
results suggest that the physiologic increase in alveolar PO2 at
birth is, at least in part, responsible for distal lung's permanent
switch from Cl secretion to Na absorption at birth.
Received 4 December 1995; accepted in final form 19 March 1996.
APS Manuscript Number L356-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 April 96