The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake

Autores
Purtell, Kerry; Paroder-Belenitsky, Monika; Reyna-Neyra, Andrea; Nicola, Juan Pablo; Koba, Wade; Fine, Eugene; Carrasco, Nancy; Abbott, Geoffrey W.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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. © FASEB.
Fil: Purtell, Kerry. Weill Cornell Medical College; Estados Unidos
Fil: Paroder-Belenitsky, Monika. Yeshiva University; Estados Unidos
Fil: Reyna-Neyra, Andrea. Yeshiva University; Estados Unidos
Fil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. University of Yale; Estados Unidos
Fil: Koba, Wade. Yeshiva University; Estados Unidos
Fil: Fine, Eugene. Yeshiva University; Estados Unidos
Fil: Carrasco, Nancy. Yeshiva University; Estados Unidos. University of Yale; Estados Unidos
Fil: Abbott, Geoffrey W.. Weill Cornell Medical College; Estados Unidos
Materia
Hypothyroidism
Kv7.1
Mirp1
Positron Emission Tomography
Sodium/Iodide Symporter
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/54966
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/54966
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptakePurtell, KerryParoder-Belenitsky, MonikaReyna-Neyra, AndreaNicola, Juan PabloKoba, WadeFine, EugeneCarrasco, NancyAbbott, Geoffrey W.HypothyroidismKv7.1Mirp1Positron Emission TomographySodium/Iodide Symporterhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The 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. © FASEB.Fil: Purtell, Kerry. Weill Cornell Medical College; Estados UnidosFil: Paroder-Belenitsky, Monika. Yeshiva University; Estados UnidosFil: Reyna-Neyra, Andrea. Yeshiva University; Estados UnidosFil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. University of Yale; Estados UnidosFil: Koba, Wade. Yeshiva University; Estados UnidosFil: Fine, Eugene. Yeshiva University; Estados UnidosFil: Carrasco, Nancy. Yeshiva University; Estados Unidos. University of Yale; Estados UnidosFil: Abbott, Geoffrey W.. Weill Cornell Medical College; Estados UnidosFederation of American Societies for Experimental Biology2012-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/54966Purtell, Kerry; Paroder-Belenitsky, Monika; Reyna-Neyra, Andrea; Nicola, Juan Pablo; Koba, Wade; et al.; The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake; Federation of American Societies for Experimental Biology; FASEB Journal; 26; 8; 8-2012; 3252-32590892-66381530-6860CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.fasebj.org/doi/10.1096/fj.12-206110info:eu-repo/semantics/altIdentifier/doi/10.1096/fj.12-206110info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:49:29Zoai:ri.conicet.gov.ar:11336/54966instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:49:29.771CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake
title The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake
spellingShingle The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake
Purtell, Kerry
Hypothyroidism
Kv7.1
Mirp1
Positron Emission Tomography
Sodium/Iodide Symporter
title_short The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake
title_full The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake
title_fullStr The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake
title_full_unstemmed The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake
title_sort The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake
dc.creator.none.fl_str_mv Purtell, Kerry
Paroder-Belenitsky, Monika
Reyna-Neyra, Andrea
Nicola, Juan Pablo
Koba, Wade
Fine, Eugene
Carrasco, Nancy
Abbott, Geoffrey W.
author Purtell, Kerry
author_facet Purtell, Kerry
Paroder-Belenitsky, Monika
Reyna-Neyra, Andrea
Nicola, Juan Pablo
Koba, Wade
Fine, Eugene
Carrasco, Nancy
Abbott, Geoffrey W.
author_role author
author2 Paroder-Belenitsky, Monika
Reyna-Neyra, Andrea
Nicola, Juan Pablo
Koba, Wade
Fine, Eugene
Carrasco, Nancy
Abbott, Geoffrey W.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hypothyroidism
Kv7.1
Mirp1
Positron Emission Tomography
Sodium/Iodide Symporter
topic Hypothyroidism
Kv7.1
Mirp1
Positron Emission Tomography
Sodium/Iodide Symporter
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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. © FASEB.
Fil: Purtell, Kerry. Weill Cornell Medical College; Estados Unidos
Fil: Paroder-Belenitsky, Monika. Yeshiva University; Estados Unidos
Fil: Reyna-Neyra, Andrea. Yeshiva University; Estados Unidos
Fil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. University of Yale; Estados Unidos
Fil: Koba, Wade. Yeshiva University; Estados Unidos
Fil: Fine, Eugene. Yeshiva University; Estados Unidos
Fil: Carrasco, Nancy. Yeshiva University; Estados Unidos. University of Yale; Estados Unidos
Fil: Abbott, Geoffrey W.. Weill Cornell Medical College; Estados Unidos
description 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. © FASEB.
publishDate 2012
dc.date.none.fl_str_mv 2012-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/54966
Purtell, Kerry; Paroder-Belenitsky, Monika; Reyna-Neyra, Andrea; Nicola, Juan Pablo; Koba, Wade; et al.; The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake; Federation of American Societies for Experimental Biology; FASEB Journal; 26; 8; 8-2012; 3252-3259
0892-6638
1530-6860
CONICET Digital
CONICET
url http://hdl.handle.net/11336/54966
identifier_str_mv Purtell, Kerry; Paroder-Belenitsky, Monika; Reyna-Neyra, Andrea; Nicola, Juan Pablo; Koba, Wade; et al.; The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake; Federation of American Societies for Experimental Biology; FASEB Journal; 26; 8; 8-2012; 3252-3259
0892-6638
1530-6860
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.fasebj.org/doi/10.1096/fj.12-206110
info:eu-repo/semantics/altIdentifier/doi/10.1096/fj.12-206110
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613532067299328
score 13.070432

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