Intestinal ion transport in NKCC1-deficient mice
Year: 2025
Type: article
Abstract: The Na+-K+-2Cl- cotransporter (NKCC1) located on the basolateral membrane of intestinal epithelia has been postulated to be the major basolateral Cl- entry pathway. With targeted mutagenesis, mice deficient in the NKCC1 protein were generated. The basal short-circuit current did not differ between normal and NKCC1 -/- jejuna. In the -/- jejuna, the forskolin response (22 μA/cm2; bumetanide insensitive) was significantly attenuated compared with the bumetanide-sensitive response (52 μA/cm2) in normal tissue. Ion-replacement studies demonstrated that the forskolin response in the NKCC1 -/- jejuna was HCO3/- dependent, whereas in the normal jejuna it was independent of the HCO3/- concentration in the buffer. NKCC1 -/- ceca exhibited a forskolin response that did not differ significantly from that of normal ceca, but unlike that of normal ceca, was bumetanide insensitive. Ion-substitution studies suggested that basolateral HCO3/- as well as Cl- entry (via non-NKCC1) paths played a role in the NKCC1 -/- secretory response. In contrast to cystic fibrosis mice, which lack both basal and stimulated Cl- secretion and exhibit severe intestinal pathology, the absence of intestinal pathology in NKCC1 -/- mice likely reflects the ability of the intestine to secrete HCO3/- and Cl- by basolateral entry mechanisms independent of NKCC1.
DOI: 10.17615/v02h-6336
Authors: Grubb B.R., Pace A.J., Koller B.H., Lee E., Boucher R.C.
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4416219506
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