Hypothyroidism of gene-targeted mice lacking Kcnq1

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. © 2010 Springer-Verlag.