The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake

Kerry Purtell, Monika Paroder-Belenitsky, Andrea Reyna-Neyra, Juan P. Nicola, Wade Koba, Eugene Fine, Nancy Carrasco, Geoffrey W. Abbott

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The KCNQ1 α subunit and the KCNE2 βsubunit 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 (EC50: 99±10 μM 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 ClO4- 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.

Original languageEnglish (US)
Pages (from-to)3252-3259
Number of pages8
JournalFASEB Journal
Volume26
Issue number8
DOIs
StatePublished - Aug 2012

Keywords

  • Hypothyroidism
  • Kv7.1
  • MiRP1
  • Positron emission tomography
  • Sodium/iodide symporter

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'The KCNQ1-KCNE2 K<sup>+</sup> channel is required for adequate thyroid I<sup>-</sup> uptake'. Together they form a unique fingerprint.

  • Cite this

    Purtell, K., Paroder-Belenitsky, M., Reyna-Neyra, A., Nicola, J. P., Koba, W., Fine, E., Carrasco, N., & Abbott, G. W. (2012). The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake. FASEB Journal, 26(8), 3252-3259. https://doi.org/10.1096/fj.12-206110