ArticleThe Journal of physiology2003
Expression and regulation of the Na+-K+-2Cl- cotransporter NKCC1 in the normal and CFTR-deficient murine colon.
Article in The Journal of physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- Distinct Roles of SLC26A3 and CFTR in Surface pH Regulation and Bicarbonate Secretion in Human Intestinal Epithelium.Acta physiologica (Oxford, England) · 2026Article
- The enigmatic SLC26A6 multifunctional anion transporter: recent advances in structure-function relationship, pathophysiological significance and novel pharmacological inhibitors.Frontiers in pharmacology · 2024Review
- Dietary NaCellular and molecular life sciences : CMLS · 2023Article
- Human Colonoid-Myofibroblast Coculture for Study of Apical NaInternational journal of molecular sciences · 2023Article
- Control of Ion Transport by Tmem16a Expressed in Murine Intestine.Frontiers in physiology · 2019Article
- Article
- TNFα induced up-regulation of NaScientific reports · 2017Article
- The ZnBiochimica et biophysica acta. Molecular basis of disease · 2017Article
- Cytokine-Regulation of NaFrontiers in immunology · 2017Review
- Potassium Channelopathies and Gastrointestinal Ulceration.Gut and liver · 2016Review
- Aquaporin 4 as a NH3 Channel.The Journal of biological chemistry · 2016Article
- Characterization of Na+-K+-2Cl- Cotransporter Activity in Rabbit Lacrimal Gland Duct Cells.Investigative ophthalmology & visual science · 2016Article
- Carbachol-induced colonic mucus formation requires transport via NKCC1, K⁺ channels and CFTR.Pflugers Archiv : European journal of physiology · 2015Article
- Cell-specific effects of luminal acid, bicarbonate, cAMP, and carbachol on transporter trafficking in the intestine.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
- Physiological relevance of cell-specific distribution patterns of CFTR, NKCC1, NBCe1, and NHE3 along the crypt-villus axis in the intestine.American journal of physiology. Gastrointestinal and liver physiology · 2011Article
- Loss of PDZ-adaptor protein NHERF2 affects membrane localization and cGMP- and [Ca2+]- but not cAMP-dependent regulation of Na+/H+ exchanger 3 in murine intestine.The Journal of physiology · 2010Article
- Defective jejunal and colonic salt absorption and alteredNa(+)/H (+) exchanger 3 (NHE3) activity in NHE regulatory factor 1 (NHERF1) adaptor protein-deficient mice.Pflugers Archiv : European journal of physiology · 2009Article
- Dynamic and differential regulation of NKCC1 by calcium and cAMP in the native human colonic epithelium.The Journal of physiology · 2007Article
- Cyclic nucleotides induce long-term augmentation of glutamate-activated chloride current in molluscan neurons.Cellular and molecular neurobiology · 2005Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defective regulation and/or reduced expression of the Na+-K+-2Cl- cotransporter NKCC1 may contribute to the severe secretory defect that is observed in cystic fibrosis, but data concerning the expression and function of NKCC1 in cystic fibrosis transmembrane conductance regulator (CFTR)-deficient cells are equivocal. We therefore investigated NKCC1 mRNA expression, Na+-K+-2Cl- cotransport activity and regulation by cAMP in crypts isolated from the proximal colon of CFTR-containing (CFTR (+/+)) and CFTR-deficient (CFTR (-/-)) mice. mRNA expression levels were determined by semiquantitative PCR, transport rates were measured fluorometrically in 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein acetomethylester (BCECF)-loaded crypts, cytoplasmic volume changes were assessed by confocal microscopy, and [Cl-]i changes were examined by N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) quenching. NKCC1 mRNA expression levels were not significantly reduced in CFTR (-/-) crypts compared to controls. Azosemide-sensitive NH4+ influx (used as a measure of Na+-K+-2Cl- cotransport) was 2.23 +/- 0.72 vs. 1.56 +/- 0.16 mM min-1, and increased by 63.6 % in (+/+) and 87.3 % in (-/-) crypts upon stimulation for 5 min with forskolin. After 20 min of stimulation with forskolin, the Na+-K+-2Cl- cotransport rates in (-/-) and (+/+) crypts were identical. Crypt cross-sectional area and [Cl-]i decreased only in (+/+) crypts upon stimulation. In conclusion, normal NKCC1 expression levels, somewhat reduced Na+-K+-2Cl- cotransport rates, but preserved activation by cAMP were found in colonic crypts from CFTR (-/-) mice, ruling out a severe dysfunction of the Na+-K+-2Cl- cotransporter in the CF intestine. Furthermore, these studies establish the existence of a direct, cell-volume- and [Cl-]i-independent activation of colonic NKCC1 by an increase in intracellular cAMP.
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