Hypothyroidism of gene-targeted mice lacking Kcnq1.
Hypothyroidism of gene-targeted mice lacking Kcnq1.
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DOI：
10.1007/s00424-010-0890-5
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发表时间：
2011-01
影响因子：
4.5
通讯作者：
Lang, Florian
中科院分区：
文献类型：
--
作者：
Froehlich, Henning;Boini, Krishna M.;Seebohm, Guiscard;Strutz-Seebohm, Nathalie;Ureche, Oana N.;Foeller, Michael;Eichenmueller, Melanie;Shumilina, Ekaterina;Pathare, Ganesh;Singh, Anurag Kumar;Seidler, Ursula;Pfeifer, Karl E.;Lang, Florian
甲状腺激素T3/T4参与发育和表现的微调。甲状腺激素的形成需要I-−通过生电的Na+/I-−同向转运体积累，这依赖于细胞膜上的电化学梯度，从而依赖于K+通道的活性。本文探讨了广泛表达的电压门控性钾通道KCNQ1是否参与了甲状腺功能的调节。为此，通过逆转录聚合酶链式反应、共聚焦显微镜检测KCNQ1基因缺陷小鼠(KCNQ1−/−)及其野生型窝种(KCNQ1+/+)的甲状腺功能。此外，还测定了KCNQ1在甲状腺FRTL-5细胞系中的丰度和电流。此外，在人甲状腺组织中还发现了编码KCNQ1及其亚基KCNE1-5的mRNA。膜片钳实验表明，促甲状腺激素(10μ/ml)可诱导FRTL-5细胞电压门控性钾电流，该作用可被钾通道阻断剂色满酚(10 mU/ml)所抑制。尽管KCNQ1TSH血浆浓度有高于KCNQ1+/+小鼠的趋势，但KCNQ1KCNQ1−/−小鼠的T3和T4血浆浓度显著低于KCNQ1KCNQ1+/+小鼠。此外，KCNQ1−/−小鼠的体温明显低于KCNQ1+/+小鼠。总之，KCNQ1是甲状腺正常功能所必需的。
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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影响因子：
6.1
作者：
Kunz, L.;Roggors, C.;Mayerhofer, A.
通讯作者：
Mayerhofer, A.
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5.5
作者：
Lan, Wen-Zhi;Wang, Penny Y. T.;Hill, Ceredwyn E.
通讯作者：
Hill, Ceredwyn E.
影响因子：
64.8
作者：
Sanguinetti, MC;Curran, ME;Keating, MT
通讯作者：
Keating, MT
影响因子：
30.8
作者：
Neyroud, N;Tesson, F;Guicheney, P
通讯作者：
Guicheney, P