Preston, Patricia and Wartosch, Lena and Guenzel, Dorothee and Fromm, Michael and Kongsuphol, Patthara and Ousingsawat, Jiraporn and Kunzelmann, Karl and Barhanin, Jacques and Warth, Richard and Jentsch, Thomas J. (2010) Disruption of the K+ Channel beta-Subunit KCNE3 Reveals an Important Role in Intestinal and Tracheal Cl- Transport. JOURNAL OF BIOLOGICAL CHEMISTRY, 285 (10). pp. 7165-7175. ISSN 0021-9258,
Full text not available from this repository. (Request a copy)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 displayed neither 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LANGE-NIELSEN-SYNDROME; LONG QT SYNDROME; GASTRIC-ACID-SECRETION; RAT DISTAL COLON; POTASSIUM CHANNEL; PERIODIC PARALYSIS; CYSTIC-FIBROSIS; I-KS; CHLORIDE SECRETION; MOUSE MODEL; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Aug 2020 11:25 |
| Last Modified: | 03 Aug 2020 11:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24984 |
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