Hypothyroidism of gene-targeted mice lacking Kcnq1

• Published in: Pflügers Archiv 2011-01, Vol.461 (1), p.45-52
• Main Authors: Fröhlich, Henning, Boini, Krishna M., Seebohm, Guiscard, Strutz-Seebohm, Nathalie, Ureche, Oana N., Föller, Michael, Eichenmüller, Melanie, Shumilina, Ekaterina, Pathare, Ganesh, Singh, Anurag Kumar, Seidler, Ursula, Pfeifer, Karl E., Lang, Florian
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Body Temperature - drug effects; Body Temperature - physiology; Cell Biology; Chromans - pharmacology; Female; Human Physiology; Humans; Hypothyroidism - genetics; Hypothyroidism - physiopathology; Immunohistochemistry; Integrative Physiology; KCNQ1 Potassium Channel - biosynthesis; KCNQ1 Potassium Channel - deficiency; KCNQ1 Potassium Channel - genetics; Male; Mice; Molecular Medicine; Neurosciences; Receptors; RNA, Messenger - metabolism; Thyroid Gland - metabolism; Thyrotropin - blood; Thyroxine - blood; Triiodothyronine - blood
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-010-0890-5

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.