The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus

Autores
Tzingounis, Anastassios V.; Heidenreich, Matthias; Kharkovets,Tatjana; Spitzmaul, Guillermo Federico; Jensen, Henrik S.; Roger, A. Nicoll; Jentsch, Thomas J.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mutations in KCNQ2 and KCNQ3 voltage-gated potassium channels lead to neonatal epilepsy as a consequence of their key role in regulating neuronal excitability. Previous studies in the brain have focused primarily on these KCNQ family members, which contribute to M-currents and afterhyperpolarization conductances in multiple brain areas. In contrast, the function of KCNQ5 (Kv7.5), which also displays widespread expression in the brain, is entirely unknown. Here, we developed mice that carry a dominant negative mutation in the KCNQ5 pore to probe whetherit has a similar function as other KCNQ channels. This mutation renders KCNQ5dn-containing homomeric and heteromeric channels nonfunctional. We find that Kcnq5dn/dn mice are viable and have normal brain morphology. Furthermore, expression and neuronal localization of KCNQ2 and KCNQ3 subunits are unchanged. However, in the CA3 area of hippocampus, a region that highly expresses KCNQ5 channels, the medium and slow afterhyperpolarization currents are significantly reduced. In contrast, neither current is affected in the CA1 area of the hippocampus, a region with low KCNQ5 expression. Our results demonstrate that KCNQ5 channels contribute to the afterhyperpolarization currents in hippocampus in a cell type-specific manner.
Fil: Tzingounis, Anastassios V.. University of California; Estados Unidos
Fil: Heidenreich, Matthias. Leibniz-Institut für Molekulare Pharmakologie; Alemania. Max-Delbrück-Centrum für Molekulare Medizin; Alemania
Fil: Kharkovets,Tatjana. Universitat Hamburg; Alemania
Fil: Spitzmaul, Guillermo Federico. Max-Delbrück-Centrum für Molekulare Medizin; Alemania. Leibniz-Institut für Molekulare Pharmakologie; Alemania
Fil: Jensen, Henrik S.. Universidad de Copenhagen; Dinamarca
Fil: Roger, A. Nicoll. University of California; Estados Unidos
Fil: Jentsch, Thomas J.. Max-Delbrück-Centrum für Molekulare Medizin; Alemania. Leibniz-Institut für Molekulare Pharmakologie; Alemania
Materia
Calcium
Epilepsy
Kcnq
M-Current
Sahp
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:11336/76672
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/76672
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampusTzingounis, Anastassios V.Heidenreich, MatthiasKharkovets,TatjanaSpitzmaul, Guillermo FedericoJensen, Henrik S.Roger, A. NicollJentsch, Thomas J.CalciumEpilepsyKcnqM-CurrentSahphttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mutations in KCNQ2 and KCNQ3 voltage-gated potassium channels lead to neonatal epilepsy as a consequence of their key role in regulating neuronal excitability. Previous studies in the brain have focused primarily on these KCNQ family members, which contribute to M-currents and afterhyperpolarization conductances in multiple brain areas. In contrast, the function of KCNQ5 (Kv7.5), which also displays widespread expression in the brain, is entirely unknown. Here, we developed mice that carry a dominant negative mutation in the KCNQ5 pore to probe whetherit has a similar function as other KCNQ channels. This mutation renders KCNQ5dn-containing homomeric and heteromeric channels nonfunctional. We find that Kcnq5dn/dn mice are viable and have normal brain morphology. Furthermore, expression and neuronal localization of KCNQ2 and KCNQ3 subunits are unchanged. However, in the CA3 area of hippocampus, a region that highly expresses KCNQ5 channels, the medium and slow afterhyperpolarization currents are significantly reduced. In contrast, neither current is affected in the CA1 area of the hippocampus, a region with low KCNQ5 expression. Our results demonstrate that KCNQ5 channels contribute to the afterhyperpolarization currents in hippocampus in a cell type-specific manner.Fil: Tzingounis, Anastassios V.. University of California; Estados UnidosFil: Heidenreich, Matthias. Leibniz-Institut für Molekulare Pharmakologie; Alemania. Max-Delbrück-Centrum für Molekulare Medizin; AlemaniaFil: Kharkovets,Tatjana. Universitat Hamburg; AlemaniaFil: Spitzmaul, Guillermo Federico. Max-Delbrück-Centrum für Molekulare Medizin; Alemania. Leibniz-Institut für Molekulare Pharmakologie; AlemaniaFil: Jensen, Henrik S.. Universidad de Copenhagen; DinamarcaFil: Roger, A. Nicoll. University of California; Estados UnidosFil: Jentsch, Thomas J.. Max-Delbrück-Centrum für Molekulare Medizin; Alemania. Leibniz-Institut für Molekulare Pharmakologie; AlemaniaNational Academy of Sciences2010-06-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/76672Tzingounis, Anastassios V.; Heidenreich, Matthias; Kharkovets,Tatjana; Spitzmaul, Guillermo Federico; Jensen, Henrik S.; et al.; The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 107; 22; 1-6-2010; 10232-102370027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/107/22/10232info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1004644107info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:00:31Zoai:ri.conicet.gov.ar:11336/76672instacron: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:34982025-10-15 15:00:32.252CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus
title The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus
spellingShingle The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus
Tzingounis, Anastassios V.
Calcium
Epilepsy
Kcnq
M-Current
Sahp
title_short The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus
title_full The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus
title_fullStr The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus
title_full_unstemmed The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus
title_sort The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus
dc.creator.none.fl_str_mv Tzingounis, Anastassios V.
Heidenreich, Matthias
Kharkovets,Tatjana
Spitzmaul, Guillermo Federico
Jensen, Henrik S.
Roger, A. Nicoll
Jentsch, Thomas J.
author Tzingounis, Anastassios V.
author_facet Tzingounis, Anastassios V.
Heidenreich, Matthias
Kharkovets,Tatjana
Spitzmaul, Guillermo Federico
Jensen, Henrik S.
Roger, A. Nicoll
Jentsch, Thomas J.
author_role author
author2 Heidenreich, Matthias
Kharkovets,Tatjana
Spitzmaul, Guillermo Federico
Jensen, Henrik S.
Roger, A. Nicoll
Jentsch, Thomas J.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Calcium
Epilepsy
Kcnq
M-Current
Sahp
topic Calcium
Epilepsy
Kcnq
M-Current
Sahp
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Mutations in KCNQ2 and KCNQ3 voltage-gated potassium channels lead to neonatal epilepsy as a consequence of their key role in regulating neuronal excitability. Previous studies in the brain have focused primarily on these KCNQ family members, which contribute to M-currents and afterhyperpolarization conductances in multiple brain areas. In contrast, the function of KCNQ5 (Kv7.5), which also displays widespread expression in the brain, is entirely unknown. Here, we developed mice that carry a dominant negative mutation in the KCNQ5 pore to probe whetherit has a similar function as other KCNQ channels. This mutation renders KCNQ5dn-containing homomeric and heteromeric channels nonfunctional. We find that Kcnq5dn/dn mice are viable and have normal brain morphology. Furthermore, expression and neuronal localization of KCNQ2 and KCNQ3 subunits are unchanged. However, in the CA3 area of hippocampus, a region that highly expresses KCNQ5 channels, the medium and slow afterhyperpolarization currents are significantly reduced. In contrast, neither current is affected in the CA1 area of the hippocampus, a region with low KCNQ5 expression. Our results demonstrate that KCNQ5 channels contribute to the afterhyperpolarization currents in hippocampus in a cell type-specific manner.
Fil: Tzingounis, Anastassios V.. University of California; Estados Unidos
Fil: Heidenreich, Matthias. Leibniz-Institut für Molekulare Pharmakologie; Alemania. Max-Delbrück-Centrum für Molekulare Medizin; Alemania
Fil: Kharkovets,Tatjana. Universitat Hamburg; Alemania
Fil: Spitzmaul, Guillermo Federico. Max-Delbrück-Centrum für Molekulare Medizin; Alemania. Leibniz-Institut für Molekulare Pharmakologie; Alemania
Fil: Jensen, Henrik S.. Universidad de Copenhagen; Dinamarca
Fil: Roger, A. Nicoll. University of California; Estados Unidos
Fil: Jentsch, Thomas J.. Max-Delbrück-Centrum für Molekulare Medizin; Alemania. Leibniz-Institut für Molekulare Pharmakologie; Alemania
description Mutations in KCNQ2 and KCNQ3 voltage-gated potassium channels lead to neonatal epilepsy as a consequence of their key role in regulating neuronal excitability. Previous studies in the brain have focused primarily on these KCNQ family members, which contribute to M-currents and afterhyperpolarization conductances in multiple brain areas. In contrast, the function of KCNQ5 (Kv7.5), which also displays widespread expression in the brain, is entirely unknown. Here, we developed mice that carry a dominant negative mutation in the KCNQ5 pore to probe whetherit has a similar function as other KCNQ channels. This mutation renders KCNQ5dn-containing homomeric and heteromeric channels nonfunctional. We find that Kcnq5dn/dn mice are viable and have normal brain morphology. Furthermore, expression and neuronal localization of KCNQ2 and KCNQ3 subunits are unchanged. However, in the CA3 area of hippocampus, a region that highly expresses KCNQ5 channels, the medium and slow afterhyperpolarization currents are significantly reduced. In contrast, neither current is affected in the CA1 area of the hippocampus, a region with low KCNQ5 expression. Our results demonstrate that KCNQ5 channels contribute to the afterhyperpolarization currents in hippocampus in a cell type-specific manner.
publishDate 2010
dc.date.none.fl_str_mv 2010-06-01
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/11336/76672
Tzingounis, Anastassios V.; Heidenreich, Matthias; Kharkovets,Tatjana; Spitzmaul, Guillermo Federico; Jensen, Henrik S.; et al.; The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 107; 22; 1-6-2010; 10232-10237
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/76672
identifier_str_mv Tzingounis, Anastassios V.; Heidenreich, Matthias; Kharkovets,Tatjana; Spitzmaul, Guillermo Federico; Jensen, Henrik S.; et al.; The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 107; 22; 1-6-2010; 10232-10237
0027-8424
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.pnas.org/content/107/22/10232
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1004644107
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 National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
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_ 1846083144635121664
score 13.22299

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