| First Author | Preston P | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 10 | Pages | 7165-75 |
| PubMed ID | 20051516 | Mgi Jnum | J:160721 |
| Mgi Id | MGI:4454978 | Doi | 10.1074/jbc.M109.047829 |
| Citation | Preston P, et al. (2010) Disruption of the K+ channel beta-subunit KCNE3 reveals an important role in intestinal and tracheal Cl- transport. J Biol Chem 285(10):7165-75 |
| abstractText | 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. |
