Alterations in airway ion transport in NKCC1-deficient mice.
Airways of Na(+)-K(+)-2Cl(-) (NKCC1)-deficient mice (-/-) were studied in Ussing chambers to determine the role of the basolateral NKCC1 in transepithelial anion secretion. The basal short-circuit current (I(sc)) of tracheae and bronchi from adult mice did not differ between NKCC1-/- and normal mice, whereas NKCC1-/- tracheae from neonatal mice exhibited a significantly reduced basal I(sc). In normal mouse tracheae, sensitivity to the NKCC1 inhibitor bumetanide correlated inversely with the age of the mouse. In contrast, tracheae from NKCC1-/- mice at all ages were insensitive to bumetanide. The anion secretory response to forskolin did not differ between normal and NKCC1-/- tissues. However, when larger anion secretory responses were induced with UTP, airways from the NKCC1-/- mice exhibited an attenuated response. Ion substitution and drug treatment protocols suggested that HCO secretion compensated for reduced Cl(-) secretion in NKCC1-/- airway epithelia. The absence of spontaneous airway disease or pathology in airways from the NKCC1-/- mice suggests that the NKCC1 mutant mice are able to compensate adequately for absence of the NKCC1 protein.
Grubb
B R
BR
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, North Carolina 27599-7248, USA. bgrubb@med.unc.edu
Pace
A J
AJ
Lee
E
E
Koller
B H
BH
Boucher
R C
RC
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D001980:Bronchi / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004553:Electric Conductivity; D066298:In Vitro Techniques; D007477:Ions; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D012016:Reference Values; D028021:Sodium-Potassium-Chloride Symporters; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D002352:Carrier Proteins; D007477:Ions; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide