Hypothyroidism of gene-targeted mice lacking Kcnq1

Pflugers Arch. 2011 Jan;461(1):45-52. doi: 10.1007/s00424-010-0890-5. Epub 2010 Oct 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Chromans / pharmacology
  • Female
  • Humans
  • Hypothyroidism / genetics*
  • Hypothyroidism / physiopathology
  • Immunohistochemistry
  • KCNQ1 Potassium Channel / biosynthesis
  • KCNQ1 Potassium Channel / deficiency
  • KCNQ1 Potassium Channel / genetics*
  • Male
  • Mice
  • RNA, Messenger / metabolism
  • Thyroid Gland / metabolism
  • Thyrotropin / blood
  • Thyroxine / blood
  • Triiodothyronine / blood

Substances

  • Chromans
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Kcnq1 protein, mouse
  • RNA, Messenger
  • Triiodothyronine
  • Thyrotropin
  • 2,2,5,7,8-pentamethyl-1-hydroxychroman
  • Thyroxine