TY - JOUR
T1 - The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake
AU - Purtell, Kerry
AU - Paroder-Belenitsky, Monika
AU - Reyna-Neyra, Andrea
AU - Nicola, Juan P.
AU - Koba, Wade
AU - Fine, Eugene
AU - Carrasco, Nancy
AU - Abbott, Geoffrey W.
PY - 2012/8
Y1 - 2012/8
N2 - The KCNQ1 α subunit and the KCNE2 βsubunit form a potassium channel in thyroid epithelial cells. Genetic disruption of KCNQ1-KCNE2 causes hypothyroidism in mice, resulting in cardiac hypertrophy, dwarfism, alopecia, and prenatal mortality. Here, we investigated the mechanistic requirement for KCNQ1-KCNE2 in thyroid hormone biosynthesis, utilizing whole-animal dynamic positron emission tomography. The KCNQ1-specific antagonist (-)-[3R,4S]- chromanol 293B (C293B) significantly impaired thyroid cell I- uptake, which is mediated by the Na+/I- symporter (NIS), in vivo (dSUV/dt: vehicle, 0.028±0.004 min-1; 10 mg/kg C293B, 0.009±0.006 min-1) and in vitro (EC50: 99±10 μM C293B). Na+-dependent nicotinate uptake by SMCT, however, was unaffected. Kcne2 deletion did not alter the balance of free vs. thyroglobulin-bound I- in the thyroid (distinguished using ClO 4-, a competitive inhibitor of NIS), indicating that KCNQ1-KCNE2 is not required for Duox/TPO-mediated I- organification. However, Kcne2 deletion doubled the rate of free I- efflux from the thyroid following ClO4- injection, a NIS-independent process. Thus, KCNQ1-KCNE2 is necessary for adequate thyroid cell I- uptake, the most likely explanation being that it is prerequisite for adequate NIS activity.
AB - The KCNQ1 α subunit and the KCNE2 βsubunit form a potassium channel in thyroid epithelial cells. Genetic disruption of KCNQ1-KCNE2 causes hypothyroidism in mice, resulting in cardiac hypertrophy, dwarfism, alopecia, and prenatal mortality. Here, we investigated the mechanistic requirement for KCNQ1-KCNE2 in thyroid hormone biosynthesis, utilizing whole-animal dynamic positron emission tomography. The KCNQ1-specific antagonist (-)-[3R,4S]- chromanol 293B (C293B) significantly impaired thyroid cell I- uptake, which is mediated by the Na+/I- symporter (NIS), in vivo (dSUV/dt: vehicle, 0.028±0.004 min-1; 10 mg/kg C293B, 0.009±0.006 min-1) and in vitro (EC50: 99±10 μM C293B). Na+-dependent nicotinate uptake by SMCT, however, was unaffected. Kcne2 deletion did not alter the balance of free vs. thyroglobulin-bound I- in the thyroid (distinguished using ClO 4-, a competitive inhibitor of NIS), indicating that KCNQ1-KCNE2 is not required for Duox/TPO-mediated I- organification. However, Kcne2 deletion doubled the rate of free I- efflux from the thyroid following ClO4- injection, a NIS-independent process. Thus, KCNQ1-KCNE2 is necessary for adequate thyroid cell I- uptake, the most likely explanation being that it is prerequisite for adequate NIS activity.
KW - Hypothyroidism
KW - Kv7.1
KW - MiRP1
KW - Positron emission tomography
KW - Sodium/iodide symporter
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U2 - 10.1096/fj.12-206110
DO - 10.1096/fj.12-206110
M3 - Article
C2 - 22549510
AN - SCOPUS:84864751054
SN - 0892-6638
VL - 26
SP - 3252
EP - 3259
JO - FASEB Journal
JF - FASEB Journal
IS - 8
ER -