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- Title
Hypothyroidism of gene-targeted mice lacking Kcnq1.
- Authors
Fröhlich, Henning; Boini, Krishna; Seebohm, Guiscard; Strutz-Seebohm, Nathalie; Ureche, Oana; Föller, Michael; Eichenmüller, Melanie; Shumilina, Ekaterina; Pathare, Ganesh; Singh, Anurag; Seidler, Ursula; Pfeifer, Karl; Lang, Florian
- Abstract
Thyroid hormones T3/T4 participate in the fine tuning of development and performance. The formation of thyroid hormones requires the accumulation of I by the electrogenic Na/I symporter, which depends on the electrochemical gradient across the cell membrane and thus on K channel activity. The present paper explored whether Kcnq1, a widely expressed voltage-gated K channel, participates in the regulation of thyroid function. To this end, Kcnq1 expression was determined by RT-PCR, confocal microscopy, and thyroid function analyzed in Kcnq1 deficient mice ( Kcnq1) and their wild-type littermates ( Kcnq1). Moreover, Kcnq1 abundance and current were determined in the thyroid FRTL-5 cell line. Furthermore, mRNA encoding KCNQ1 and the subunits KCNE1-5 were discovered in human thyroid tissue. According to patch-clamp TSH (10 mUnits/ml) induced a voltage-gated K current in FRTL-5 cells, which was inhibited by the Kcnq inhibitor chromanol (10 μM). Despite a tendency of TSH plasma concentrations to be higher in Kcnq1 than in Kcnq1 mice, the T3 and T4 plasma concentrations were significantly smaller in Kcnq1 than in Kcnq1 mice. Moreover, body temperature was significantly lower in Kcnq1 than in Kcnq1 mice. In conclusion, Kcnq1 is required for proper function of thyroid glands.
- Subjects
HYPOTHYROIDISM; THYROID hormones; CELL membranes; POTASSIUM channels; THYROID gland; MESSENGER RNA; GENE expression; CELL lines; BODY temperature; LABORATORY mice
- Publication
Pflügers Archiv: European Journal of Physiology, 2011, Vol 461, Issue 1, p45
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-010-0890-5