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Hypothyroidism of gene-targeted mice lacking Kcnq1

  • Integrative Physiology
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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.

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Acknowledgements

The authors acknowledge the technical assistance of E. Faber, R. Engelhardt, B. Rausch, and Dr. B. Riederer for breeding and genotyping kcnq1 −/− and kcnq1 +/+ mice. The manuscript was meticulously prepared by T. Loch and L. Subasic. This study was supported by the Deutsche Forschungsgemeinschaft (GK 1302) and Se460/9-6 (to U.S.).

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Authors and Affiliations

  1. Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Henning Fröhlich, Krishna M. Boini, Oana N. Ureche, Michael Föller, Melanie Eichenmüller, Ekaterina Shumilina, Ganesh Pathare & Florian Lang

  2. Department of Biochemistry I, Ruhr-University Bochum, Universitaetsstrasse 150, 44780, Bochum, Germany

    Guiscard Seebohm & Nathalie Strutz-Seebohm

  3. Department of Molecular Pathology, University of Tübingen, Tübingen, Germany

    Oana N. Ureche

  4. Department of Gastroenterology, Hepatology, and Endocrinology, Medical University Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Anurag Kumar Singh & Ursula Seidler

  5. Laboratory of Mammalian Genes and Development, NICHD/National Institutes of Health, Bethesda, MD, USA

    Karl E. Pfeifer

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  1. Henning Fröhlich
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  2. Krishna M. Boini
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Correspondence to Florian Lang.

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Henning Fröhlich, Krishna M. Boini, and Guiscard Seebohm contributed equally and thus share first authorship.

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Fröhlich, H., Boini, K.M., Seebohm, G. et al. Hypothyroidism of gene-targeted mice lacking Kcnq1. Pflugers Arch - Eur J Physiol 461, 45–52 (2011). https://doi.org/10.1007/s00424-010-0890-5

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  • DOI: https://doi.org/10.1007/s00424-010-0890-5

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