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 mediat ed by the sodium-potassium-2-Cl- cotransporter NKCC1. We studied the role o f NKCC1 in Cl- and liquid secretion in late-gestation NKCC-null (-/-) and l ittermate 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 w as 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 contr ol 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 hy perpolarization was less in NKCC -/- than in control tracheas (,BPD: contro l, -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 le vels in the fetal NKCC -/- mouse lung.