Alterations in airway ion transport in NKCC1-deficient mice

Am J Physiol Cell Physiol. 2001 Aug;281(2):C615-23. doi: 10.1152/ajpcell.2001.281.2.C615.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / physiology
  • Animals
  • Animals, Newborn / growth & development
  • Animals, Newborn / physiology
  • Biological Transport / physiology
  • Bronchi / metabolism
  • Bumetanide / pharmacology
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Electric Conductivity
  • In Vitro Techniques
  • Ions
  • Mice
  • Mice, Knockout / genetics
  • Reference Values
  • Sodium-Potassium-Chloride Symporters
  • Trachea / drug effects
  • Trachea / metabolism*
  • Trachea / physiology


  • Carrier Proteins
  • Ions
  • Sodium-Potassium-Chloride Symporters
  • Bumetanide