title: Increased Po2 alters the bioelectric properties of fetal distal lung epithelium.
abstract: At birth the lung must efficiently clear the liquid from its air spaces and permanently convert from a fluid-secreting to a fluid-absorbing organ. When primary cultures of rat fetal distal lung epithelium (FDLE) 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 (Rt) 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 Rt 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 = NS). Changes in Rt were associated with expected changes in the histological appearance of the interepithelial 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 -gamma rat epithelial Na channel mRNA increased within 48 h of increasing the ambient oxygen concentration. These results suggest that the physiological 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.
authors.affiliation: Hospital for Sick Children's Research Institute's Respiratory Research Division, University of Toronto, Ontario, Canada.
authors.forename: O
authors.initials: O
authors.lastname: Pitkänen
authors.forename: A K
authors.initials: AK
authors.lastname: Tanswell
authors.forename: G
authors.initials: G
authors.lastname: Downey
authors.forename: H
authors.initials: H
authors.lastname: O'Brodovich
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002478:Cells, Cultured; D002712:Chlorides / Q000502:physiology; D017097:Electric Impedance; D004594:Electrophysiology; D004847:Epithelial Cells; D004848:Epithelium / Q000196:embryology / Q000502:physiology; D005333:Fetus / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D010100:Oxygen; D010313:Partial Pressure; D051381:Rats / Q000196:embryology; D017208:Rats, Wistar; D012964:Sodium / Q000502:physiology; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D002712:Chlorides; D015222:Sodium Channels; D012964:Sodium; D010100:Oxygen