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| 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., Wartosch, L., Guenzel, D., Fromm, M., Kongsuphol, P., Ousingsawat, J., Kunzelmann, K., Barhanin, J., 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 |
| 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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