| First Author | Purtell K | Year | 2012 |
| Journal | FASEB J | Volume | 26 |
| Issue | 8 | Pages | 3252-9 |
| PubMed ID | 22549510 | Mgi Jnum | J:187467 |
| Mgi Id | MGI:5437169 | Doi | 10.1096/fj.12-206110 |
| Citation | Purtell K, et al. (2012) The KCNQ1-KCNE2 K(+) channel is required for adequate thyroid I(-) uptake. FASEB J 26(8):3252-9 |
| abstractText | The KCNQ1 alpha subunit and the KCNE2 beta subunit form a potassium channel in thyroid epithelial cells. Genetic disruption of KCNQ1-KCNE2 causes hypothyroidism in mice, resulting in cardiac hypertrophy, dwarfism, alopecia, and prenatal mortality. Here, we investigated the mechanistic requirement for KCNQ1-KCNE2 in thyroid hormone biosynthesis, utilizing whole-animal dynamic positron emission tomography. The KCNQ1-specific antagonist (-)-[3R,4S]-chromanol 293B (C293B) significantly impaired thyroid cell I(-) uptake, which is mediated by the Na(+)/I(-) symporter (NIS), in vivo (dSUV/dt: vehicle, 0.028 +/- 0.004 min(-1); 10 mg/kg C293B, 0.009 +/- 0.006 min(-1)) and in vitro (EC(50): 99 +/- 10 muM C293B). Na(+)-dependent nicotinate uptake by SMCT, however, was unaffected. Kcne2 deletion did not alter the balance of free vs. thyroglobulin-bound I(-) in the thyroid (distinguished using ClO(4)(-), a competitive inhibitor of NIS), indicating that KCNQ1-KCNE2 is not required for Duox/TPO-mediated I(-) organification. However, Kcne2 deletion doubled the rate of free I(-) efflux from the thyroid following ClO(4)(-) injection, a NIS-independent process. Thus, KCNQ1-KCNE2 is necessary for adequate thyroid cell I(-) uptake, the most likely explanation being that it is prerequisite for adequate NIS activity. |
