No abstract

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.

No abstract

To determine if pulmonary oedema fluid (EF) alters ion and fluid transport of distal lung epithelium (DLE), EF was collected from rats in acute heart failure. EF, but not plasma, increased amiloride‐insensitive short circuit current (Isc) and Na+‐K+ ATPase protein content and pump activity of DLE grown in primary culture. Inhibitors of Cl− transport or cGMP‐gated cation channels had a significant (P < 0.05), but limited ability to block the increased Isc. EF increased amiloride‐insensitive, but not amiloride‐sensitive, DLE apical membrane Na+ conductance. The level of mRNA encoding epithelial sodium channel (ENaC) subunits was unchanged (α, β), or decreased (γ, P < 0.05) in EF‐exposed DLE. EF also induced an amiloride‐insensitive increase in the potential difference across murine tracheal cysts. Distal lung explants from late gestation wild‐type and α‐ENaC‐deficient fetal mice, which normally expand due to liquid secretion, decreased in size due to liquid absorption when exposed to EF. Trypsin digestion or heat treatment of EF abrogated the ability of EF to increase amiloride‐insensitive Isc in DLE and liquid absorption by distal lung explants. Thus proteins or protein‐dependent factors within cardiogenic EF induce an α‐ENaC‐independent and amiloride‐insensitive apical membrane Na+ conductance and liquid absorption in the distal lung.