Department of Anesthesiology

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

TitleThe KCNQ1-KCNE2 K⁺ channel is required for adequate thyroid I⁻ uptake.
Publication TypeJournal Article
Year of Publication2012
AuthorsPurtell K, Paroder-Belenitsky M, Reyna-Neyra A, Nicola JP, Koba W, Fine E, Carrasco N, Abbott GW
JournalFASEB J
Volume26
Issue8
Pagination3252-9
Date Published2012 Aug
ISSN1530-6860
KeywordsAnimals, Cercopithecus aethiops, COS Cells, Humans, Hypothyroidism, Iodides, KCNQ1 Potassium Channel, Mice, Positron-Emission Tomography, Potassium Channels, Voltage-Gated, Symporters, Thyroid Gland
Abstract

The KCNQ1 α subunit and the KCNE2 β 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 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 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.

DOI10.1096/fj.12-206110
Alternate JournalFASEB J.
PubMed ID22549510
PubMed Central IDPMC3405278
Grant List5T32GM002788 / GM / NIGMS NIH HHS / United States
DK41544 / DK / NIDDK NIH HHS / United States
HL079275 / HL / NHLBI NIH HHS / United States
R01 HL079275 / HL / NHLBI NIH HHS / United States
T32 GM007288 / GM / NIGMS NIH HHS / United States
T32GM073546 / GM / NIGMS NIH HHS / United States