Liquid and ion transport by fetal airway and lung epithelia of mice deficient in sodium-potassium-2-chloride transporter.
Chloride (Cl(-)) movement across fetal lung epithelia is thought to be mediated by the sodium-potassium-2-Cl(-) cotransporter NKCC1. We studied the role of NKCC1 in Cl(-) and liquid secretion in late-gestation NKCC-null (-/-) and littermate control fetal mouse lung. NKCC -/- mice had decreased lung water compared with littermate controls (wet/dry: control, 8.01 +/- 0.09; NKCC -/-, 7.06 +/- 0.14). Liquid secretion by 17-d NKCC -/- distal lung explants was similar to control explants. Bumetanide inhibited basal liquid secretion in control but not NKCC -/- explants (expansion over 48 h: control, 35 +/- 4%; NKCC -/- 46 +/- 7%). Treatment with 4,4'-diisothiocyanto-stilbene-2,2'-disulfonic acid (DIDS) decreased liquid secretion in both control and NKCC -/- explants. Basal transepithelial potential difference (PD) of control tracheal explants was higher than that of NKCC -/- (control, -13.7 +/- 0.5 mV; NKCC -/-, -11.6 +/- 0.6 mV). Amiloride (10(-)(4) M) inhibited basal PD to the same extent in control and NKCC -/- mice. Terbutaline-stimulated hyperpolarization was less in NKCC -/- than in control tracheas (DeltaPD: control, -10.8 +/- 1.33 mV; NKCC -/-, -6.1 +/- 0.7 mV) and was inhibited by DIDS and acetazolamide in NKCC -/- but not wild-type explants. We conclude that NKCC is rate-limiting for transcellular Cl(-) transport, and that alternative anion transport mechanisms can sustain liquid production at near-normal levels in the fetal NKCC -/- mouse lung.
Gillie
D J
DJ
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Pace
A J
AJ
Coakley
R J
RJ
Koller
B H
BH
Barker
P M
PM
D000818:Animals; D002254:Carbonates / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D004847:Epithelial Cells / Q000378:metabolism; D005838:Genotype; D006863:Hydrogen-Ion Concentration; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D017136:Ion Transport; D050356:Lipid Metabolism; D008168:Lung / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D028021:Sodium-Potassium-Chloride Symporters; D014132:Trachea / Q000166:cytology / Q000196:embryology / Q000378:metabolism*
D002254:Carbonates; D002352:Carrier Proteins; D002712:Chlorides; D028021:Sodium-Potassium-Chloride Symporters