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.
Department of Physiology, University of Tübingen, Gmelinstrasse 5, Tübingen, Germany.
Henning
H
Fröhlich
Krishna M
KM
Boini
Guiscard
G
Seebohm
Nathalie
N
Strutz-Seebohm
Oana N
ON
Ureche
Michael
M
Föller
Melanie
M
Eichenmüller
Ekaterina
E
Shumilina
Ganesh
G
Pathare
Anurag Kumar
AK
Singh
Ursula
U
Seidler
Karl E
KE
Pfeifer
Florian
F
Lang
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002839:Chromans / Q000494:pharmacology; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics* / Q000503:physiopathology; D007150:Immunohistochemistry; D051657:KCNQ1 Potassium Channel / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D002839:Chromans; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C496910:Kcnq1 protein, mouse; D012333:RNA, Messenger; D014284:Triiodothyronine; D013972:Thyrotropin; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman; D013974:Thyroxine