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Disruption of the K+ channel beta-subunit KCNE3 reveals an important role in intestinal and tracheal Cl- transport

Item Type:Article
Title:Disruption of the K+ channel beta-subunit KCNE3 reveals an important role in intestinal and tracheal Cl- transport
Creators Name:Preston, P. and Wartosch, L. and Guenzel, D. and Fromm, M. and Kongsuphol, P. and Ousingsawat, J. and Kunzelmann, K. and Barhanin, J. and Warth, R. and Jentsch, T.J.
Abstract:The KCNE3 beta-subunit constitutively opens outwardly-rectifying KCNQ1 (Kv7.1) K+ channels by abolishing their voltage-dependent gating. The resulting KCNQ1/KCNE3 heteromers display enhanced sensitivity to K+ channel inhibitors like chromanol 293B. KCNE3 was also suggested to modify biophysical properties of several other K+ channels and a mutation in KCNE3 was proposed to underlie forms of human periodic paralysis. To investigate physiological roles of KCNE3, we now disrupted its gene in mice. Kcne3-/- mice were viable and fertile and did neither display periodic paralysis nor other obvious skeletal muscle abnormalities. KCNQ1/KCNE3 heteromers are present in basolateral membranes of intestinal and tracheal epithelial cells where they might facilitate transepithelial Cl- secretion through basolateral recycling of K+ ions and by increasing the electrochemical driving force for apical Cl- exit. Indeed, cAMP-stimulated electrogenic Cl- secretion across tracheal and intestinal epithelia was drastically reduced in kcne3-/- mice. Because the abundance and subcellular localization of KCNQ1 was unchanged in kcne3-/- mice, the modification of biophysical properties of KCNQ1 by KCNE3 is essential for its role in intestinal and tracheal transport. Further, these results suggest KCNE3 as a potential modifier gene in cystic fibrosis.
Keywords:Chloride Transport, Epithelium, Gene Knockout, Intestine, Potassium Channels, CFTR, KCNN4, KvLQT1, MiRP2, Ussing Chamber, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:285
Number:10
Page Range:7165-7175
Date:5 March 2010
Official Publication:https://doi.org/10.1074/jbc.M109.047829
PubMed:View item in PubMed

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