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

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

Research output: Contribution to journalArticle

31 Citations (Scopus)

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

Fingerprint

Symporters
Thyroid Gland
Dwarfism
Positron emission tomography
Thyroglobulin
Niacin
Potassium Channels
Biosynthesis
Alopecia
Cardiomegaly
Hypothyroidism
Thyroid Hormones
Positron-Emission Tomography
Animals
Injections
Mortality
6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Purtell, K., Paroder-Belenitsky, M., Reyna-Neyra, A., Nicola, J. P., Koba, W. R., Fine, E., ... 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

The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake. / Purtell, Kerry; Paroder-Belenitsky, Monika; Reyna-Neyra, Andrea; Nicola, Juan P.; Koba, Wade R.; Fine, Eugene; Carrasco, Nancy; Abbott, Geoffrey W.

In: FASEB Journal, Vol. 26, No. 8, 08.2012, p. 3252-3259.

Research output: Contribution to journalArticle

Purtell, K, Paroder-Belenitsky, M, Reyna-Neyra, A, Nicola, JP, Koba, WR, Fine, E, Carrasco, N & Abbott, GW 2012, 'The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake', FASEB Journal, vol. 26, no. 8, pp. 3252-3259. https://doi.org/10.1096/fj.12-206110
Purtell K, Paroder-Belenitsky M, Reyna-Neyra A, Nicola JP, Koba WR, Fine E et al. The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake. FASEB Journal. 2012 Aug;26(8):3252-3259. https://doi.org/10.1096/fj.12-206110
Purtell, Kerry ; Paroder-Belenitsky, Monika ; Reyna-Neyra, Andrea ; Nicola, Juan P. ; Koba, Wade R. ; Fine, Eugene ; Carrasco, Nancy ; Abbott, Geoffrey W. / The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake. In: FASEB Journal. 2012 ; Vol. 26, No. 8. pp. 3252-3259.
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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.",
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